                         SEQUENCE LISTING

<110>  Beijing Biocytogen Co., Ltd.
 
<120>  GENETICALLY MODIFIED NON-HUMAN ANIMAL WITH HUMAN OR CHIMERIC MHC 
       PROTEIN COMPLEX

<130>  1

<160>  68    

<170>  PatentIn version 3.5

<210>  1
<211>  858
<212>  DNA
<213>  Mus musculus

<400>  1
tttcagtggc tgctactcgg cgcttcagtc gcggtcgctt cagtcgtcag catggctcgc       60

tcggtgaccc tggtctttct ggtgcttgtc tcactgaccg gcctgtatgc tatccagaaa      120

acccctcaaa ttcaagtata ctcacgccac ccaccggaga atgggaagcc gaacatactg      180

aactgctacg taacacagtt ccacccgcct cacattgaaa tccaaatgct gaagaacggg      240

aaaaaaattc ctaaagtaga gatgtcagat atgtccttca gcaaggactg gtctttctat      300

atcctggctc acactgaatt cacccccact gagactgata catacgcctg cagagttaag      360

catgccagta tggccgagcc caagaccgtc tactgggatc gagacatgtg atcaagcatc      420

atgatgctct gaagattcat ttgaacctgc ttaattacaa atccagtttc taatatgcta      480

tacaatttat gcacgcagaa agaaatagca atgtacacat caccttcttt atatcttact      540

ttaaatattt tatgcatgtt ttcaaaaaat tggaaatatc ctagatagct gagcaataaa      600

tcttcaataa gtattttgat cagaataata aatataattt taagaacaat agttgatcat      660

atgccaaacc ctctgtactt ctcattactt ggatgcagtt actcatcttt ggtctatcac      720

aacataagtg acatactttc cttttggtaa agcaaagagg cctaattgaa gtctgtcact      780

gtgcccaatg cttagcaatt ctcaccccca accctgtggc tacttctgct tttgttactt      840

ttactaaaaa taaaaaac                                                    858


<210>  2
<211>  119
<212>  PRT
<213>  Mus musculus

<400>  2

Met Ala Arg Ser Val Thr Leu Val Phe Leu Val Leu Val Ser Leu Thr 
1               5                   10                  15      


Gly Leu Tyr Ala Ile Gln Lys Thr Pro Gln Ile Gln Val Tyr Ser Arg 
            20                  25                  30          


His Pro Pro Glu Asn Gly Lys Pro Asn Ile Leu Asn Cys Tyr Val Thr 
        35                  40                  45              


Gln Phe His Pro Pro His Ile Glu Ile Gln Met Leu Lys Asn Gly Lys 
    50                  55                  60                  


Lys Ile Pro Lys Val Glu Met Ser Asp Met Ser Phe Ser Lys Asp Trp 
65                  70                  75                  80  


Ser Phe Tyr Ile Leu Ala His Thr Glu Phe Thr Pro Thr Glu Thr Asp 
                85                  90                  95      


Thr Tyr Ala Cys Arg Val Lys His Ala Ser Met Ala Glu Pro Lys Thr 
            100                 105                 110         


Val Tyr Trp Asp Arg Asp Met 
        115                 


<210>  3
<211>  1675
<212>  DNA
<213>  Homo sapiens

<400>  3
attcctgaag ctgacagcat tcgggccgag atgtctcgct ccgtggcctt agctgtgctc       60

gcgctactct ctctttctgg cctggaggct atccagcgta ctccaaagat tcaggtttac      120

tcacgtcatc cagcagagaa tggaaagtca aatttcctga attgctatgt gtctgggttt      180

catccatccg acattgaagt tgacttactg aagaatggag agagaattga aaaagtggag      240

cattcagact tgtctttcag caaggactgg tctttctatc tcttgtacta cactgaattc      300

acccccactg aaaaagatga gtatgcctgc cgtgtgaacc atgtgacttt gtcacagccc      360

aagatagtta agtgggatcg agacatgtaa gcagcatcat ggaggtttga agatgccgca      420

tttggattgg atgaattcca aattctgctt gcttgctttt taatattgat atgcttatac      480

acttacactt tatgcacaaa atgtagggtt ataataatgt taacatggac atgatcttct      540

ttataattct actttgagtg ctgtctccat gtttgatgta tctgagcagg ttgctccaca      600

ggtagctcta ggagggctgg caacttagag gtggggagca gagaattctc ttatccaaca      660

tcaacatctt ggtcagattt gaactcttca atctcttgca ctcaaagctt gttaagatag      720

ttaagcgtgc ataagttaac ttccaattta catactctgc ttagaatttg ggggaaaatt      780

tagaaatata attgacagga ttattggaaa tttgttataa tgaatgaaac attttgtcat      840

ataagattca tatttacttc ttatacattt gataaagtaa ggcatggttg tggttaatct      900

ggtttatttt tgttccacaa gttaaataaa tcataaaact tgatgtgtta tctcttatat      960

ctcactccca ctattacccc tttattttca aacagggaaa cagtcttcaa gttccacttg     1020

gtaaaaaatg tgaacccctt gtatatagag tttggctcac agtgtaaagg gcctcagtga     1080

ttcacatttt ccagattagg aatctgatgc tcaaagaagt taaatggcat agttggggtg     1140

acacagctgt ctagtgggag gccagccttc tatattttag ccagcgttct ttcctgcggg     1200

ccaggtcatg aggagtatgc agactctaag agggagcaaa agtatctgaa ggatttaata     1260

ttttagcaag gaatagatat acaatcatcc cttggtctcc ctgggggatt ggtttcagga     1320

ccccttcttg gacaccaaat ctatggatat ttaagtccct tctataaaat ggtatagtat     1380

ttgcatataa cctatccaca tcctcctgta tactttaaat catttctaga ttacttgtaa     1440

tacctaatac aatgtaaatg ctatgcaaat agttgttatt gtttaaggaa taatgacaag     1500

aaaaaaaagt ctgtacatgc tcagtaaaga cacaaccatc cctttttttc cccagtgttt     1560

ttgatccatg gtttgctgaa tccacagatg tggagcccct ggatacggaa ggcccgctgt     1620

actttgaatg acaaataaca gatttaaaat tttcaaggca tagttttata cctga          1675


<210>  4
<211>  119
<212>  PRT
<213>  Homo sapiens

<400>  4

Met Ser Arg Ser Val Ala Leu Ala Val Leu Ala Leu Leu Ser Leu Ser 
1               5                   10                  15      


Gly Leu Glu Ala Ile Gln Arg Thr Pro Lys Ile Gln Val Tyr Ser Arg 
            20                  25                  30          


His Pro Ala Glu Asn Gly Lys Ser Asn Phe Leu Asn Cys Tyr Val Ser 
        35                  40                  45              


Gly Phe His Pro Ser Asp Ile Glu Val Asp Leu Leu Lys Asn Gly Glu 
    50                  55                  60                  


Arg Ile Glu Lys Val Glu His Ser Asp Leu Ser Phe Ser Lys Asp Trp 
65                  70                  75                  80  


Ser Phe Tyr Leu Leu Tyr Tyr Thr Glu Phe Thr Pro Thr Glu Lys Asp 
                85                  90                  95      


Glu Tyr Ala Cys Arg Val Asn His Val Thr Leu Ser Gln Pro Lys Ile 
            100                 105                 110         


Val Lys Trp Asp Arg Asp Met 
        115                 


<210>  5
<211>  1736
<212>  DNA
<213>  Mus musculus

<400>  5
tcagacaccc gggatcccag atgggggcga tggctccgcg cacgctgctc ctgctgctgg       60

cggccgccct ggccccgact cagacccgcg cgggcccaca ctcgatgcgg tatttcgaga      120

ccgccgtgtc ccggcccggc ctcgaggagc cccggtacat ctctgtcggc tatgtggaca      180

acaaggagtt cgtgcgcttc gacagcgacg cggagaatcc gagatatgag ccgcgggcgc      240

cgtggatgga gcaggagggg ccggagtatt gggagcggga aacacagaaa gccaagggcc      300

aagagcagtg gttccgagtg agcctgagga acctgctcgg ctactacaac cagagcgcgg      360

gcggctctca cacactccag cagatgtctg gctgtgactt ggggtcggac tggcgcctcc      420

tccgcgggta cctgcagttc gcctatgaag gccgcgatta catcgccctg aacgaagacc      480

tgaaaacgtg gacggcggcg gacatggcgg cgcagatcac ccgacgcaag tgggagcaga      540

gtggtgctgc agagcattac aaggcctacc tggagggcga gtgcgtggag tggctccaca      600

gatacctgaa gaacgggaac gcgacgctgc tgcgcacaga ttccccaaag gcacatgtga      660

cccatcaccc cagatctaaa ggtgaagtca ccctgaggtg ctgggccctg ggcttctacc      720

ctgctgacat caccctgacc tggcagttga atggggagga gctgacccag gacatggagc      780

ttgtggagac caggcctgca ggggatggaa ccttccagaa gtgggcatct gtggtggtgc      840

ctcttgggaa ggagcagaat tacacatgcc gtgtgtacca tgaggggctg cctgagcccc      900

tcaccctgag atgggagcct cctccgtcca ctgactctta catggtgatc gttgctgttc      960

tgggtgtcct tggagctatg gccatcattg gagctgtggt ggcttttgtg atgaagagaa     1020

ggagaaacac aggtggaaaa ggaggggact atgctctggc tccaggctcc cagagctctg     1080

aaatgtctct ccgagattgt aaagcgtgaa gacagctgcc tggactgtac tgagtgacag     1140

acgatgtgtt caggtctctc ctgtgacatc cagagccctc agttctcttt acacaacatt     1200

gtctgatgtt ccctgtgagc ttgggttcag tgtgaagaac tgtggagccc agcctgccct     1260

gcacaccagg accctatccc tgcactgccc tgtgttccct tccatagcca accttgctgc     1320

tccagccaaa cactggggga catctgcatc ctgtaagctc catgctaccc tgagctgcag     1380

ctcctcactt ccacactgag aataataatt tgaatgtggg tggctggaga gatggctcag     1440

cgctgactgc tcttccaaag gtcctgagtt caaatcccag caaccacatg gtggctcaca     1500

accatctgta atgggatcta acaccctctt ctgcagtgtc tgaagacagc tacagtgtac     1560

ttacatataa taataaataa gtctttaaaa aataatttga aagtgacctt gattgttaac     1620

atcttgatct agggctgatt tcttgttaat ttcatggatt gagaatgctt agaggttttt     1680

ttgtttgttt gattgatttt tttgaagaaa taaatggcag atgaaggaac ttccag         1736


<210>  6
<211>  362
<212>  PRT
<213>  Mus musculus

<400>  6

Met Gly Ala Met Ala Pro Arg Thr Leu Leu Leu Leu Leu Ala Ala Ala 
1               5                   10                  15      


Leu Ala Pro Thr Gln Thr Arg Ala Gly Pro His Ser Met Arg Tyr Phe 
            20                  25                  30          


Glu Thr Ala Val Ser Arg Pro Gly Leu Glu Glu Pro Arg Tyr Ile Ser 
        35                  40                  45              


Val Gly Tyr Val Asp Asn Lys Glu Phe Val Arg Phe Asp Ser Asp Ala 
    50                  55                  60                  


Glu Asn Pro Arg Tyr Glu Pro Arg Ala Pro Trp Met Glu Gln Glu Gly 
65                  70                  75                  80  


Pro Glu Tyr Trp Glu Arg Glu Thr Gln Lys Ala Lys Gly Gln Glu Gln 
                85                  90                  95      


Trp Phe Arg Val Ser Leu Arg Asn Leu Leu Gly Tyr Tyr Asn Gln Ser 
            100                 105                 110         


Ala Gly Gly Ser His Thr Leu Gln Gln Met Ser Gly Cys Asp Leu Gly 
        115                 120                 125             


Ser Asp Trp Arg Leu Leu Arg Gly Tyr Leu Gln Phe Ala Tyr Glu Gly 
    130                 135                 140                 


Arg Asp Tyr Ile Ala Leu Asn Glu Asp Leu Lys Thr Trp Thr Ala Ala 
145                 150                 155                 160 


Asp Met Ala Ala Gln Ile Thr Arg Arg Lys Trp Glu Gln Ser Gly Ala 
                165                 170                 175     


Ala Glu His Tyr Lys Ala Tyr Leu Glu Gly Glu Cys Val Glu Trp Leu 
            180                 185                 190         


His Arg Tyr Leu Lys Asn Gly Asn Ala Thr Leu Leu Arg Thr Asp Ser 
        195                 200                 205             


Pro Lys Ala His Val Thr His His Pro Arg Ser Lys Gly Glu Val Thr 
    210                 215                 220                 


Leu Arg Cys Trp Ala Leu Gly Phe Tyr Pro Ala Asp Ile Thr Leu Thr 
225                 230                 235                 240 


Trp Gln Leu Asn Gly Glu Glu Leu Thr Gln Asp Met Glu Leu Val Glu 
                245                 250                 255     


Thr Arg Pro Ala Gly Asp Gly Thr Phe Gln Lys Trp Ala Ser Val Val 
            260                 265                 270         


Val Pro Leu Gly Lys Glu Gln Asn Tyr Thr Cys Arg Val Tyr His Glu 
        275                 280                 285             


Gly Leu Pro Glu Pro Leu Thr Leu Arg Trp Glu Pro Pro Pro Ser Thr 
    290                 295                 300                 


Asp Ser Tyr Met Val Ile Val Ala Val Leu Gly Val Leu Gly Ala Met 
305                 310                 315                 320 


Ala Ile Ile Gly Ala Val Val Ala Phe Val Met Lys Arg Arg Arg Asn 
                325                 330                 335     


Thr Gly Gly Lys Gly Gly Asp Tyr Ala Leu Ala Pro Gly Ser Gln Ser 
            340                 345                 350         


Ser Glu Met Ser Leu Arg Asp Cys Lys Ala 
        355                 360         


<210>  7
<211>  1611
<212>  DNA
<213>  Homo sapiens

<400>  7
gagaagccaa tcagtgtcgt cgcggtcgct gttctaaagt ccgcacgcac ccaccgggac       60

tcagattctc cccagacgcc gaggatggcc gtcatggcgc cccgaaccct cctcctgcta      120

ctctcggggg ccctggccct gacccagacc tgggcgggct cccactccat gaggtatttc      180

ttcacatccg tgtcccggcc cggccgcggg gagccccgct tcatcgccgt gggctacgtg      240

gacgacacgc agttcgtgcg gttcgacagc gacgccgcga gccagaagat ggagccgcgg      300

gcgccgtgga tagagcagga ggggccggag tattgggacc aggagacacg gaatatgaag      360

gcccactcac agactgaccg agcgaacctg gggaccctgc gcggctacta caaccagagc      420

gaggacggtt ctcacaccat ccagataatg tatggctgcg acgtggggcc ggacgggcgc      480

ttcctccgcg ggtaccggca ggacgcctac gacggcaagg attacatcgc cctgaacgag      540

gacctgcgct cttggaccgc ggcggacatg gcagctcaga tcaccaagcg caagtgggag      600

gcggtccatg cggcggagca gcggagagtc tacctggagg gccggtgcgt ggacgggctc      660

cgcagatacc tggagaacgg gaaggagacg ctgcagcgca cggacccccc caagacacat      720

atgacccacc accccatctc tgaccatgag gccaccctga ggtgctgggc cctgggcttc      780

taccctgcgg agatcacact gacctggcag cgggatgggg aggaccagac ccaggacacg      840

gagctcgtgg agaccaggcc tgcaggggat ggaaccttcc agaagtgggc ggctgtggtg      900

gtgccttctg gagaggagca gagatacacc tgccatgtgc agcatgaggg tctgcccaag      960

cccctcaccc tgagatggga gctgtcttcc cagcccacca tccccatcgt gggcatcatt     1020

gctggcctgg ttctccttgg agctgtgatc actggagctg tggtcgctgc cgtgatgtgg     1080

aggaggaaga gctcagatag aaaaggaggg agttacactc aggctgcaag cagtgacagt     1140

gcccagggct ctgatgtgtc tctcacagct tgtaaagtgt gagacagctg ccttgtgtgg     1200

gactgagagg caagagttgt tcctgccctt ccctttgtga cttgaagaac cctgactttg     1260

tttctgcaaa ggcacctgca tgtgtctgtg ttcgtgtagg cataatgtga ggaggtgggg     1320

agagcacccc acccccatgt ccaccatgac cctcttccca cgctgacctg tgctccctct     1380

ccaatcatct ttcctgttcc agagaggtgg ggctgaggtg tctccatctc tgtctcaact     1440

tcatggtgca ctgagctgta acttcttcct tccctattaa aattagaacc tgagtataaa     1500

tttactttct caaattcttg ccatgagagg ttgatgagtt aattaaagga gaagattcct     1560

aaaatttgag agacaaaatt aatggaacgc atgagaacct tccagagtcc a              1611


<210>  8
<211>  365
<212>  PRT
<213>  Homo sapiens

<400>  8

Met Ala Val Met Ala Pro Arg Thr Leu Leu Leu Leu Leu Ser Gly Ala 
1               5                   10                  15      


Leu Ala Leu Thr Gln Thr Trp Ala Gly Ser His Ser Met Arg Tyr Phe 
            20                  25                  30          


Phe Thr Ser Val Ser Arg Pro Gly Arg Gly Glu Pro Arg Phe Ile Ala 
        35                  40                  45              


Val Gly Tyr Val Asp Asp Thr Gln Phe Val Arg Phe Asp Ser Asp Ala 
    50                  55                  60                  


Ala Ser Gln Lys Met Glu Pro Arg Ala Pro Trp Ile Glu Gln Glu Gly 
65                  70                  75                  80  


Pro Glu Tyr Trp Asp Gln Glu Thr Arg Asn Met Lys Ala His Ser Gln 
                85                  90                  95      


Thr Asp Arg Ala Asn Leu Gly Thr Leu Arg Gly Tyr Tyr Asn Gln Ser 
            100                 105                 110         


Glu Asp Gly Ser His Thr Ile Gln Ile Met Tyr Gly Cys Asp Val Gly 
        115                 120                 125             


Pro Asp Gly Arg Phe Leu Arg Gly Tyr Arg Gln Asp Ala Tyr Asp Gly 
    130                 135                 140                 


Lys Asp Tyr Ile Ala Leu Asn Glu Asp Leu Arg Ser Trp Thr Ala Ala 
145                 150                 155                 160 


Asp Met Ala Ala Gln Ile Thr Lys Arg Lys Trp Glu Ala Val His Ala 
                165                 170                 175     


Ala Glu Gln Arg Arg Val Tyr Leu Glu Gly Arg Cys Val Asp Gly Leu 
            180                 185                 190         


Arg Arg Tyr Leu Glu Asn Gly Lys Glu Thr Leu Gln Arg Thr Asp Pro 
        195                 200                 205             


Pro Lys Thr His Met Thr His His Pro Ile Ser Asp His Glu Ala Thr 
    210                 215                 220                 


Leu Arg Cys Trp Ala Leu Gly Phe Tyr Pro Ala Glu Ile Thr Leu Thr 
225                 230                 235                 240 


Trp Gln Arg Asp Gly Glu Asp Gln Thr Gln Asp Thr Glu Leu Val Glu 
                245                 250                 255     


Thr Arg Pro Ala Gly Asp Gly Thr Phe Gln Lys Trp Ala Ala Val Val 
            260                 265                 270         


Val Pro Ser Gly Glu Glu Gln Arg Tyr Thr Cys His Val Gln His Glu 
        275                 280                 285             


Gly Leu Pro Lys Pro Leu Thr Leu Arg Trp Glu Leu Ser Ser Gln Pro 
    290                 295                 300                 


Thr Ile Pro Ile Val Gly Ile Ile Ala Gly Leu Val Leu Leu Gly Ala 
305                 310                 315                 320 


Val Ile Thr Gly Ala Val Val Ala Ala Val Met Trp Arg Arg Lys Ser 
                325                 330                 335     


Ser Asp Arg Lys Gly Gly Ser Tyr Thr Gln Ala Ala Ser Ser Asp Ser 
            340                 345                 350         


Ala Gln Gly Ser Asp Val Ser Leu Thr Ala Cys Lys Val 
        355                 360                 365 


<210>  9
<211>  2109
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  The mRNA sequence of the engineered mouse B2M-HLA-A2.1 after 
       humanization

<400>  9
tttcagtggc tgctactcgg cgcttcagtc gcggtcgctt cagtcgtcag catggccgtc       60

atggcgcccc gaaccctcgt cctgctactc tcgggggctc tggccctgac ccagacctgg      120

gcgatccagc gtactccaaa gattcaggtt tactcacgtc atccagcaga gaatggaaag      180

tcaaatttcc tgaattgcta tgtgtctggg tttcatccat ccgacattga agttgactta      240

ctgaagaatg gagagagaat tgaaaaagtg gagcattcag acttgtcttt cagcaaggac      300

tggtctttct atctcttgta ctacactgaa ttcaccccca ctgaaaaaga tgagtatgcc      360

tgccgtgtga accatgtgac tttgtcacag cccaagatag ttaagtggga tcgagacatg      420

ggaggtggcg gatccggcgg aggcggctcg ggtggcggcg gctctggctc tcactccatg      480

aggtatttct tcacatccgt gtcccggccc ggccgcgggg agccccgctt catcgcagtg      540

ggctacgtgg acgacacgca gttcgtgcgg ttcgacagcg acgccgcgag ccagaggatg      600

gagccgcggg cgccgtggat agagcaggag ggtccggagt attgggacgg ggagacacgg      660

aaagtgaagg cccactcaca gactcaccga gtggacctgg ggaccctgcg cggctactac      720

aaccagagcg aggccggttc tcacaccgtc cagaggatgt atggctgcga cgtggggtcg      780

gactggcgct tcctccgcgg gtaccaccag tacgcctacg acggcaagga ttacatcgcc      840

ctgaaagagg acctgcgctc ttggaccgcg gcggacatgg cagctcagac caccaagcac      900

aagtgggagg cggcccatgt ggcggagcag ttgagagcct acctggaggg cacgtgcgtg      960

gagtggctcc gcagatacct ggagaacggg aaggagacgc tgcagcgcac ggattcccca     1020

aaggcacatg tgacccatca ccccagatct aaaggtgaag tcaccctgag gtgctgggcc     1080

ctgggcttct accctgctga catcaccctg acctggcagt tgaatgggga ggagctgacc     1140

caggacatgg agcttgtgga gaccaggcct gcaggggatg gaaccttcca gaagtgggca     1200

tctgtggtgg tgcctcttgg gaaggagcag aattacacat gccgtgtgta ccatgagggg     1260

ctgcctgagc ccctcaccct gagatgggag cctcctccgt ccactgactc ttacatggtg     1320

atcgttgctg ttctgggtgt ccttggagct atggccatca ttggagctgt ggtggctttt     1380

gtgatgaaga gaaggagaaa cacaggtgga aaaggagggg actatgctct ggctccaggc     1440

tcccagagct ctgaaatgtc tctccgagat tgtaaagcgt gaagacagct gcctggactg     1500

tactgagtga cagacgatgt gttcaggtct ctcctgtgac atccagagcc ctcagttctc     1560

tttacacaac attgtctgat gttccctgtg agcttgggtt cagtgtgaag aactgtggag     1620

cccagcctgc cctgcacacc aggaccctat ccctgcactg ccctgtgttc ccttccatag     1680

ccaaccttgc tgctccagcc aaacactggg ggacatctgc atcctgtaag ctccatgcta     1740

ccctgagctg cagctcctca cttccacact gagaataata atttgaatgt gggtggctgg     1800

agagatggct cagcgctgac tgctcttcca aaggtcctga gttcaaatcc cagcaaccac     1860

atggtggctc acaaccatct gtaatgggat ctaacaccct cttctgcagt gtctgaagac     1920

agctacagtg tacttacata taataataaa taagtcttta aaaaataatt tgaaagtgac     1980

cttgattgtt aacatcttga tctagggctg atttcttgtt aatttcatgg attgagaatg     2040

cttagaggtt tttttgtttg tttgattgat ttttttgaag aaataaatgg cagatgaagg     2100

aacttccag                                                             2109


<210>  10
<211>  4694
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  The DNA sequence of the engineered mouse B2M-HLA-A2.1 after 
       humanization

<400>  10
tttcagtggc tgctactcgg cgcttcagtc gcggtcgctt cagtcgtcag catggccgtc       60

atggcgcccc gaaccctcgt cctgctactc tcgggggctc tggccctgac ccagacctgg      120

gcgatccagc gtactccaaa gattcaggtt tactcacgtc atccagcaga gaatggaaag      180

tcaaatttcc tgaattgcta tgtgtctggg tttcatccat ccgacattga agttgactta      240

ctgaagaatg gagagagaat tgaaaaagtg gagcattcag acttgtcttt cagcaaggac      300

tggtctttct atctcttgta ctacactgaa ttcaccccca ctgaaaaaga tgagtatgcc      360

tgccgtgtga accatgtgac tttgtcacag cccaagatag ttaagtggga tcgagacatg      420

ggaggtggcg gatccggcgg aggcggctcg ggtggcggcg gctctggctc tcactccatg      480

aggtatttct tcacatccgt gtcccggccc ggccgcgggg agccccgctt catcgcagtg      540

ggctacgtgg acgacacgca gttcgtgcgg ttcgacagcg acgccgcgag ccagaggatg      600

gagccgcggg cgccgtggat agagcaggag ggtccggagt attgggacgg ggagacacgg      660

aaagtgaagg cccactcaca gactcaccga gtggacctgg ggaccctgcg cggctactac      720

aaccagagcg aggccggtga gtgaccccgg cccggggcgc aggtcacgac ctctcatccc      780

ccacggacgg gccaggtcgc ccacagtctc cgggtccgag atccgccccg aagccgcggg      840

accccgagac ccttgccccg ggagaggccc aggcgccttt acccggtttc attttcagtt      900

taggccaaaa atccccccag gttggtcggg gcggggcggg gctcggggga ccgggctgac      960

cgcggggtcc gggccaggtt ctcacaccgt ccagaggatg tatggctgcg acgtggggtc     1020

ggactggcgc ttcctccgcg ggtaccacca gtacgcctac gacggcaagg attacatcgc     1080

cctgaaagag gacctgcgct cttggaccgc ggcggacatg gcagctcaga ccaccaagca     1140

caagtgggag gcggcccatg tggcggagca gttgagagcc tacctggagg gcacgtgcgt     1200

ggagtggctc cgcagatacc tggagaacgg gaaggagacg ctgcagcgca cgggtaccag     1260

gggccacggg gcgcctccct gatcgcctgt agatctggat cctgtgtgac atacctgtac     1320

cttgtcctcc agagtcaggg gctgggagtc attttctctg gctacagact ttgtgatggc     1380

tgttcactcg gactgacagt taacgttggt cagcaagatg accacagtgg ttgagtctca     1440

gtggtgggac ccttccagta gcatatgccc ctaattttga tatgaactca aacagatatt     1500

aaattactta ttttccattc cctattccat tctgtgacta tctctctcat gctattgaac     1560

atcacataag gatggccatg ttcacccact ggctcatgtg gattccctct tagcttcttt     1620

gtcccaaaag aaaatgtgca gtcctgtgct gaggggacca gctctgcttt tggtcactag     1680

tgcaatgaca gtgtagtgtc aaatagacac atagttcact ctcatcattg atttaactga     1740

gtcttgtgta gatttcagtt tgtcttgtta attgtggaat ttcttaaatc ttccacacag     1800

attccccaaa ggcacatgtg acccatcacc ccagatctaa aggtgaagtc accctgaggt     1860

gctgggccct gggcttctac cctgctgaca tcaccctgac ctggcagttg aatggggagg     1920

agctgaccca ggacatggag cttgtggaga ccaggcctgc aggggatgga accttccaga     1980

agtgggcatc tgtggtggtg cctcttggga aggagcagaa ttacacatgc cgtgtgtacc     2040

atgaggggct gcctgagccc ctcaccctga gatggggtaa ggagggtgtg ggtgcagagc     2100

tggggtcagg gaaagctgga gccttctgca gaccctgagc tggtcaggga tgagagctgg     2160

ggtcataacc ctcaccttca tttcctgtac ctgtccttcc cagagcctcc tccgtccact     2220

gactcttaca tggtgatcgt tgctgttctg ggtgtccttg gagctatggc catcattgga     2280

gctgtggtgg cttttgtgat gaagagaagg agaaacacag gtaagaaagg gcagggtctg     2340

agttttctct cagcctcctt tagaagtgtg ctctgctcat taatggggaa cacagccaca     2400

ccccacattg ctactgtctc taactgggtc tgctgtcagt tctgggaatt tccagtgtca     2460

agatcttcct tgaactctca cagcttttct tttcacaggt ggaaaaggag gggactatgc     2520

tctggctcca ggttagtgtg gggacaggat tgttctgggg gacattggag tgaagttgga     2580

gatgatggga gctctgggaa tccataatag ctcctccaga gaaatcttct aggggcctga     2640

gttgtgccat gaagtgaata cattcatgta catatgcata tacatttgtt ttgttttacc     2700

ctaggctccc agagctctga aatgtctctc cgagattgta aaggtgacac tctagggtct     2760

gattggggag gggcaatgtg gacatgattg ggtttcaggg actcccagaa tctcctgaga     2820

gtgagtggtg ggttgctgga atgttgtctt cacagtgatg gttcatgact ctcattctct     2880

agcgtgaaga cagctgcctg gactgtactg agtgacagac gatgtgttca ggtctctcct     2940

gtgacatcca gagccctcag ttctctttac acaacattgt ctgatgttcc ctgtgagctt     3000

gggttcagtg tgaagaactg tggagcccag cctgccctgc acaccaggac cctatccctg     3060

cactgccctg tgttcccttc catagccaac cttgctgctc cagccaaaca ctgggggaca     3120

tctgcatcct gtaagctcca tgctaccctg agctgcagct cctcacttcc acactgagaa     3180

taataatttg aatgtgggtg gctggagaga tggctcagcg ctgactgctc ttccaaaggt     3240

cctgagttca aatcccagca accacatggt ggctcacaac catctgtaat gggatctaac     3300

accctcttct gcagtgtctg aagacagcta cagtgtactt acatataata ataaataagt     3360

ctttaaaaaa taatttgaaa gtgaccttga ttgttaacat cttgatctag ggctgatttc     3420

ttgttaattt catggattga gaatgcttag aggttttttt gtttgtttga ttgatttttt     3480

tgaagaaata aatggcagat gaaggaactt ccagaatctg ggtcactatg ctgtgtgtat     3540

ctgttgggac aggatgaggc tgtggcagct gagtgtgaac agggctgtgc ccaggtgggc     3600

tcagtccatt ttgatctgtg atggggccac acctcggctg tgtcacctct gggctctgtt     3660

ctctccatca ctctgaggca catcctgaga gtttgtgatc acaaagacac agggagggcc     3720

tgagccttgc cctgtcccca ggattatgag cccctagggc taaagatcag agactcaact     3780

aggacagagc tctgcgggta catcttagcc ctttcagtct ctagttggta ggcactagat     3840

ttaccttctg gaggcttccg gacactcagg gaaagaaatg gacagggttg taacttcatg     3900

taaggcaccg tcactgatgt gtcagaagga agttgaggag cgtgagaggg aacgtgggtg     3960

tctctgtcag gtggagtcta gtggtagaaa atccagcttt tcggtgaaat ccagggccct     4020

tgaggccaaa agctcactca aatcttgtat tatatttatt tctaggaaag gggaattgat     4080

gaagggggtg gggatgggtg atctgcccag acaagcagtt accaaatggt ggagccagaa     4140

ctcacctcct ttaagaaggt gattgtccta caaactcatt tgatggtgag gtctggaatg     4200

taaataatgt aatgttcggc taaccttctc cttctctccc tcccttcccc ttttcttttc     4260

agctctgaag attcatttga acctgcttaa ttacaaatcc agtttctaat atgctataca     4320

atttatgcac gcagaaagaa atagcaatgt acacatcacc ttctttatat cttactttaa     4380

atattttatg catgttttca aaaaattgga aatatcctag atagctgagc aataaatctt     4440

caataagtat tttgatcaga ataataaata taattttaag aacaatagtt gatcatatgc     4500

caaaccctct gtacttctca ttacttggat gcagttactc atctttggtc tatcacaaca     4560

taagtgacat actttccttt tggtaaagca aagaggccta attgaagtct gtcactgtgc     4620

ccaatgctta gcaattctca cccccaaccc tgtggctact tctgcttttg ttacttttac     4680

taaaaataaa aaac                                                       4694


<210>  11
<211>  1409
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  5' arm

<400>  11
gcatttccta gtacagttca acacagtgtt tagtataatt taatattaac atttcaggtc       60

tttaatgtat taaatgagtt tttcttttta attagatgaa gtatcttaac tcacaccttt      120

atacataaaa attattctta tatttcagtt acaaaaaggg atagcaaaat aacataaatg      180

attatgattc ttaaacatta ctggatcaaa atactatatg ctgggtagac actgtaggat      240

tgggtctctg tttattatct cattaatgtc cgtggagact attttatttt tttctagttt      300

agacacagcc tccacactag agattgttaa aggtttttaa aaatatgttc aagaaatcca      360

gaagttatgt tgttctcctt ggggaagcca aggccaaagc cacttcaact gcaagcatgg      420

ccatttctcc atgtcctgat gccccatgcc ctcttcctac ccttcctcac tcgagctgct      480

tgcggtggtg tctccctgtg ctcacagcct gcctctgtcc tggcttttgg ccaggggttt      540

aacttctcta ctgggtccac cgctgatgta atatacattc tgagtaaaac tatggcagcc      600

tttgtcttcc gagccgataa gcagaaaccc caagggaatg catctcaagg tttatctcct      660

catccagaaa aaataattta ttcggggatt cacttcactt ggtcacttag tttaccaatg      720

gccctgttct aagaaagtac tactaagaga atggacagga aacccagcta agccattgtc      780

cttccccaaa acccatggac agaacaaaga aaattaccta aatttttcaa gggtacccga      840

ttaagttctc catccaaagc tctaaaagga gaaacctgct agaagcaagg tcagaaatcc      900

tctcagttgc ctttaggaca ggagggtctt tttacacacg gaatcctgaa actgcctttg      960

tatttctggg ctgagattat aaactaaggg ttgagttctg ccagttaatg ctcttaattg     1020

tcctggcttt agttttcaag aatgcaaact tcaggtccta agtccttttc tgagtgggat     1080

attgtcagca attgaataaa tgaaggcggt cccaggctga acgaccagat acaccaaact     1140

caagagcaca ccctagatag tagggcacca agggtccagc ccaggctgtt tgaaatatca     1200

cgggacttta taagaacatg aaactgaaaa tgggaaagtc cctttgtaac ctagttcagc     1260

atcaacagct aggagactgg tgacgacctc cggatctgag tccggattgg ctgtgagttc     1320

aggaactata taagagcgcg cgccctggct ggctctcatt tcagtggctg ctactcggcg     1380

cttcagtcgc ggtcgcttca gtcgtcagc                                       1409


<210>  12
<211>  1343
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  3' arm

<400>  12
gacagagctc tgcgggtaca tcttagccct ttcagtctct agttggtagg cactagattt       60

accttctgga ggcttccgga cactcaggga aagaaatgga cagggttgta acttcatgta      120

aggcaccgtc actgatgtgt cagaaggaag ttgaggagcg tgagagggaa cgtgggtgtc      180

tctgtcaggt ggagtctagt ggtagaaaat ccagcttttc ggtgaaatcc agggcccttg      240

aggccaaaag ctcactcaaa tcttgtatta tatttatttc taggaaaggg gaattgatga      300

agggggtggg gatgggtgat ctgcccagac aagcagttac caaatggtgg agccagaact      360

cacctccttt aagaaggtga ttgtcctaca aactcatttg atggtgaggt ctggaatgta      420

aataatgtaa tgttcggcta accttctcct tctctccctc ccttcccctt ttcttttcag      480

ctctgaagat tcatttgaac ctgcttaatt acaaatccag tttctaatat gctatacaat      540

ttatgcacgc agaaagaaat agcaatgtac acatcacctt ctttatatct tactttaaat      600

attttatgca tgttttcaaa aaattggaaa tatcctagat agctgagcaa taaatcttca      660

ataagtattt tgatcagaat aataaatata attttaagaa caatagttga tcatatgcca      720

aaccctctgt acttctcatt acttggatgc agttactcat ctttggtcta tcacaacata      780

agtgacatac tttccttttg gtaaagcaaa gaggcctaat tgaagtctgt cactgtgccc      840

aatgcttagc aattctcacc cccaaccctg tggctacttc tgcttttgtt acttttacta      900

aaaataaaaa actaaaaaaa aaaaaaaaaa ttgttgccag acattgccag tgttacatga      960

agtggtttct aggtagcata aatgcctgca agcacgtgcg tatttttcat catctaaaga     1020

ggcagtgggt atcttagaag gttcttgcag aagcaggctc ctcaactaag ggtcgagagg     1080

aaagtgacta ggaaaggcct ccaaagcaga gcagtaggag gtggtgatga aggtcaggga     1140

ataataggaa gaaactgaga ggggagtgag gatctcagac gtgctggtcc cacagggagc     1200

tctagagcag agatcacatc ttacagtttg tcttggtgat gtgcacagct tgttgctggc     1260

tccacaggac tgtatgctag gatgaaagcc cagatacttt ggggtgcagg ttatggttat     1320

ggggtgcaag ttatggttat tgg                                             1343


<210>  13
<211>  72
<212>  DNA
<213>  Homo sapiens

<400>  13
atggccgtca tggcgccccg aaccctcgtc ctgctactct cgggggctct ggccctgacc       60

cagacctggg cg                                                           72


<210>  14
<211>  297
<212>  DNA
<213>  Homo sapiens

<400>  14
atccagcgta ctccaaagat tcaggtttac tcacgtcatc cagcagagaa tggaaagtca       60

aatttcctga attgctatgt gtctgggttt catccatccg acattgaagt tgacttactg      120

aagaatggag agagaattga aaaagtggag cattcagact tgtctttcag caaggactgg      180

tctttctatc tcttgtacta cactgaattc acccccactg aaaaagatga gtatgcctgc      240

cgtgtgaacc atgtgacttt gtcacagccc aagatagtta agtgggatcg agacatg         297


<210>  15
<211>  831
<212>  DNA
<213>  Homo sapiens

<400>  15
ggctctcact ccatgaggta tttcttcaca tccgtgtccc ggcccggccg cggggagccc       60

cgcttcatcg cagtgggcta cgtggacgac acgcagttcg tgcggttcga cagcgacgcc      120

gcgagccaga ggatggagcc gcgggcgccg tggatagagc aggagggtcc ggagtattgg      180

gacggggaga cacggaaagt gaaggcccac tcacagactc accgagtgga cctggggacc      240

ctgcgcggct actacaacca gagcgaggcc ggtgagtgac cccggcccgg ggcgcaggtc      300

acgacctctc atcccccacg gacgggccag gtcgcccaca gtctccgggt ccgagatccg      360

ccccgaagcc gcgggacccc gagacccttg ccccgggaga ggcccaggcg cctttacccg      420

gtttcatttt cagtttaggc caaaaatccc cccaggttgg tcggggcggg gcggggctcg      480

ggggaccggg ctgaccgcgg ggtccgggcc aggttctcac accgtccaga ggatgtatgg      540

ctgcgacgtg gggtcggact ggcgcttcct ccgcgggtac caccagtacg cctacgacgg      600

caaggattac atcgccctga aagaggacct gcgctcttgg accgcggcgg acatggcagc      660

tcagaccacc aagcacaagt gggaggcggc ccatgtggcg gagcagttga gagcctacct      720

ggagggcacg tgcgtggagt ggctccgcag atacctggag aacgggaagg agacgctgca      780

gcgcacgggt accaggggcc acggggcgcc tccctgatcg cctgtagatc t               831


<210>  16
<211>  2486
<212>  DNA
<213>  Mus musculus

<400>  16
ggatcctgtg tgacatacct gtaccttgtc ctccagagtc aggggctggg agtcattttc       60

tctggctaca gactttgtga tggctgttca ctcggactga cagttaacgt tggtcagcaa      120

gatgaccaca gtggttgagt ctcagtggtg ggacccttcc agtagcatat gcccctaatt      180

ttgatatgaa ctcaaacaga tattaaatta cttattttcc attccctatt ccattctgtg      240

actatctctc tcatgctatt gaacatcaca taaggatggc catgttcacc cactggctca      300

tgtggattcc ctcttagctt ctttgtccca aaagaaaatg tgcagtcctg tgctgagggg      360

accagctctg cttttggtca ctagtgcaat gacagtgtag tgtcaaatag acacatagtt      420

cactctcatc attgatttaa ctgagtcttg tgtagatttc agtttgtctt gttaattgtg      480

gaatttctta aatcttccac acagattccc caaaggcaca tgtgacccat caccccagat      540

ctaaaggtga agtcaccctg aggtgctggg ccctgggctt ctaccctgct gacatcaccc      600

tgacctggca gttgaatggg gaggagctga cccaggacat ggagcttgtg gagaccaggc      660

ctgcagggga tggaaccttc cagaagtggg catctgtggt ggtgcctctt gggaaggagc      720

agaattacac atgccgtgtg taccatgagg ggctgcctga gcccctcacc ctgagatggg      780

gtaaggaggg tgtgggtgca gagctggggt cagggaaagc tggagccttc tgcagaccct      840

gagctggtca gggatgagag ctggggtcat aaccctcacc ttcatttcct gtacctgtcc      900

ttcccagagc ctcctccgtc cactgactct tacatggtga tcgttgctgt tctgggtgtc      960

cttggagcta tggccatcat tggagctgtg gtggcttttg tgatgaagag aaggagaaac     1020

acaggtaaga aagggcaggg tctgagtttt ctctcagcct cctttagaag tgtgctctgc     1080

tcattaatgg ggaacacagc cacaccccac attgctactg tctctaactg ggtctgctgt     1140

cagttctggg aatttccagt gtcaagatct tccttgaact ctcacagctt ttcttttcac     1200

aggtggaaaa ggaggggact atgctctggc tccaggttag tgtggggaca ggattgttct     1260

gggggacatt ggagtgaagt tggagatgat gggagctctg ggaatccata atagctcctc     1320

cagagaaatc ttctaggggc ctgagttgtg ccatgaagtg aatacattca tgtacatatg     1380

catatacatt tgttttgttt taccctaggc tcccagagct ctgaaatgtc tctccgagat     1440

tgtaaaggtg acactctagg gtctgattgg ggaggggcaa tgtggacatg attgggtttc     1500

agggactccc agaatctcct gagagtgagt ggtgggttgc tggaatgttg tcttcacagt     1560

gatggttcat gactctcatt ctctagcgtg aagacagctg cctggactgt actgagtgac     1620

agacgatgtg ttcaggtctc tcctgtgaca tccagagccc tcagttctct ttacacaaca     1680

ttgtctgatg ttccctgtga gcttgggttc agtgtgaaga actgtggagc ccagcctgcc     1740

ctgcacacca ggaccctatc cctgcactgc cctgtgttcc cttccatagc caaccttgct     1800

gctccagcca aacactgggg gacatctgca tcctgtaagc tccatgctac cctgagctgc     1860

agctcctcac ttccacactg agaataataa tttgaatgtg ggtggctgga gagatggctc     1920

agcgctgact gctcttccaa aggtcctgag ttcaaatccc agcaaccaca tggtggctca     1980

caaccatctg taatgggatc taacaccctc ttctgcagtg tctgaagaca gctacagtgt     2040

acttacatat aataataaat aagtctttaa aaaataattt gaaagtgacc ttgattgtta     2100

acatcttgat ctagggctga tttcttgtta atttcatgga ttgagaatgc ttagaggttt     2160

ttttgtttgt ttgattgatt tttttgaaga aataaatggc agatgaagga acttccagaa     2220

tctgggtcac tatgctgtgt gtatctgttg ggacaggatg aggctgtggc agctgagtgt     2280

gaacagggct gtgcccaggt gggctcagtc cattttgatc tgtgatgggg ccacacctcg     2340

gctgtgtcac ctctgggctc tgttctctcc atcactctga ggcacatcct gagagtttgt     2400

gatcacaaag acacagggag ggcctgagcc ttgccctgtc cccaggatta tgagccccta     2460

gggctaaaga tcagagactc aactag                                          2486


<210>  17
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA1 targeting site sequence

<400>  17
cctggccaat cccgtcggga agg                                               23


<210>  18
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA2 targeting site sequence

<400>  18
ccgtcagcac actcgcaaac agg                                               23


<210>  19
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA3 targeting site sequence

<400>  19
gttctccttc ccgacgggat tgg                                               23


<210>  20
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA4 targeting site sequence

<400>  20
actctggata gcatacaggc cgg                                               23


<210>  21
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA5 targeting site sequence

<400>  21
ctggtgcttg tctcactgac cgg                                               23


<210>  22
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA6 targeting site sequence

<400>  22
ggggaaagag gcactcactc tgg                                               23


<210>  23
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA7 targeting site sequence

<400>  23
gacaagcacc agaaagacca ggg                                               23


<210>  24
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA8 targeting site sequence

<400>  24
ctggaggctt ccggacactc agg                                               23


<210>  25
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA9 targeting site sequence

<400>  25
tgatcaagca tcatgatggt agg                                               23


<210>  26
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA10 targeting site sequence

<400>  26
aggagcgtga gagggaacgt ggg                                               23


<210>  27
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA11 targeting site sequence

<400>  27
gaggaacgta gccatgtcac tgg                                               23


<210>  28
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA12 targeting site sequence

<400>  28
catgtcactg gccctctaaa ggg                                               23


<210>  29
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA13 targeting site sequence

<400>  29
catgtgatca agcatcatga tgg                                               23


<210>  30
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA14 targeting site sequence

<400>  30
acccgcagag ctctgtcact cgg                                               23


<210>  31
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA15 targeting site sequence

<400>  31
ctctgtcact cggctcctct ggg                                               23


<210>  32
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA-3 upstream sequence

<400>  32
gttctccttc ccgacgggat                                                   20


<210>  33
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA-3 forward oligonucleotide

<400>  33
taggttctcc ttcccgacgg gat                                               23


<210>  34
<211>  19
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA-3 downstream sequence

<400>  34
atcccgtcgg gaaggagaa                                                    19


<210>  35
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA-3 reverse oligonucleotide

<400>  35
aaacatcccg tcgggaagga gaa                                               23


<210>  36
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA-14 upstream sequence

<400>  36
acccgcagag ctctgtcact                                                   20


<210>  37
<211>  24
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA-14 forward oligonucleotide

<400>  37
taggacccgc agagctctgt cact                                              24


<210>  38
<211>  19
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA-14 downstream sequence

<400>  38
agtgacagac tctgcgggt                                                    19


<210>  39
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA-14 reverse oligonucleotide

<400>  39
aaacagtgac agactctgcg ggt                                               23


<210>  40
<211>  132
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  DNA fragment containing the T7 promoter and sgRNA fragment

<400>  40
gaattctaat acgactcact atagggggtc ttcgagaaga cctgttttag agctagaaat       60

agcaagttaa aataaggcta gtccgttatc aacttgaaaa agtggcaccg agtcggtgct      120

tttaaaggat cc                                                          132


<210>  41
<211>  25
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  5'end primer

<400>  41
gaatgtgtgc ctcctctcag tttcc                                             25


<210>  42
<211>  25
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  5'end primer

<400>  42
tccttcccgt tctccaggta tctgc                                             25


<210>  43
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  3'end primer

<400>  43
gcggctacta caaccagagc gag                                               23


<210>  44
<211>  27
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  3'end primer

<400>  44
tccagcaata agaaccagtc cctagct                                           27


<210>  45
<211>  25
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Probe primer

<400>  45
atgaggtctt tttgtgggca gagca                                             25


<210>  46
<211>  25
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Probe primer

<400>  46
ctccctacgg ccacatcacc attac                                             25


<210>  47
<211>  24
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Probe primer

<400>  47
taacttcatg taaggcaccg tcac                                              24


<210>  48
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Probe primer

<400>  48
tccagacctc accatcaaat gag                                               23


<210>  49
<211>  25
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  5'end primer for KO mouse

<400>  49
gaataaatga aggcggtccc aggct                                             25


<210>  50
<211>  25
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  3'end primer for KO mouse

<400>  50
aggtgagttc tggctccacc atttg                                             25


<210>  51
<211>  45
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  The flexible linker nucleotide sequence

<400>  51
ggaggtggcg gatccggcgg aggcggctcg ggtggcggcg gctct                       45


<210>  52
<211>  1891
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  mRNA sequence of humanized B-NDG mouse

<400>  52
tttcagtggc tgctactcgg cgcttcagtc gcggtcgctt cagtcgtcag catggccgtc       60

atggcgcccc gaaccctcgt cctgctactc tcgggggctc tggccctgac ccagacctgg      120

gcgatccagc gtactccaaa gattcaggtt tactcacgtc atccagcaga gaatggaaag      180

tcaaatttcc tgaattgcta tgtgtctggg tttcatccat ccgacattga agttgactta      240

ctgaagaatg gagagagaat tgaaaaagtg gagcattcag acttgtcttt cagcaaggac      300

tggtctttct atctcttgta ctacactgaa ttcaccccca ctgaaaaaga tgagtatgcc      360

tgccgtgtga accatgtgac tttgtcacag cccaagatag ttaagtggga tcgagacatg      420

ggaggtggcg gatccggcgg aggcggctcg ggtggcggcg gctctggctc tcactccatg      480

aggtatttct tcacatccgt gtcccggccc ggccgcgggg agccccgctt catcgcagtg      540

ggctacgtgg acgacacgca gttcgtgcgg ttcgacagcg acgccgcgag ccagaggatg      600

gagccgcggg cgccgtggat agagcaggag ggtccggagt attgggacgg ggagacacgg      660

aaagtgaagg cccactcaca gactcaccga gtggacctgg ggaccctgcg cggctactac      720

aaccagagcg aggccggttc tcacaccgtc cagaggatgt atggctgcga cgtggggtcg      780

gactggcgct tcctccgcgg gtaccaccag tacgcctacg acggcaagga ttacatcgcc      840

ctgaaagagg acctgcgctc ttggaccgcg gcggacatgg cagctcagac caccaagcac      900

aagtgggagg cggcccatgt ggcggagcag ttgagagcct acctggaggg cacgtgcgtg      960

gagtggctcc gcagatacct ggagaacggg aaggagacgc tgcagcgcac ggacgccccc     1020

aaaacgcata tgactcacca cgctgtctct gaccatgaag ccaccctgag gtgctgggcc     1080

ctgagcttct accctgcgga gatcacactg acctggcagc gggatgggga ggaccagacc     1140

caggacacgg agctcgtgga gaccaggcct gcaggggatg gaaccttcca gaagtgggcg     1200

gctgtggtgg tgccttctgg acaggagcag agatacacct gccatgtgca gcatgagggt     1260

ttgcccaagc ccctcaccct gagatgggag ccgtcttccc agcccaccat ccccatcgtg     1320

ggcatcattg ctggcctggt tctctttgga gctgtgatca ctggagctgt ggtcgctgct     1380

gtgatgtgga ggaggaagag ctcagataga aaaggaggga gctactctca ggctgcaagc     1440

agtgacagtg cccagggctc tgatgtgtct ctcacagctt gtaaagtgtg agacagctgc     1500

cttgtgtggg actgagaggc aagagttgtt cctgcccttc cctttgtgac ttgaagaacc     1560

ctgactttgt ttctgcaaag gcacctgcat gtgtctgtgt tcgtgtaggc ataatgtgag     1620

gaggtgggga gaccacccca cccccatgtc caccatgacc ctcttcccac gctgacctgt     1680

gctccctccc caatcatctt tcctgttcca gagaggtggg gctgaggtgt ctccatctct     1740

gtctcaactt catggtgcac tgagctgtaa cttcttcctt ccctattaaa attagaacct     1800

gagtataaat ttactttctc aaattcttgc catgagaggt tgatgagtta attaaaggag     1860

aagattccta aaatttgaga gacaaaataa a                                    1891


<210>  53
<211>  1342
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  3' arm

<400>  53
gacagagctc tgcgggtaca tcttagccct ttcagtctct agttggtagg cactagattt       60

accttctgga ggcttccgga cactcagaga aagaaatgga cagggttgta acttcatgta      120

aggcaccgtc actgatgtgt cagaaggaag ttgaggagcg tgagagggaa cgtgggtgtc      180

tctgtcaggt ggagtctagt ggtagaaaat ccagcttttc agtgaaatcc agggcccttg      240

aggccaaaag ctcactcaaa tcttgtatta tatttatttc taggaaaggg gaattgatga      300

agggggtggg gatgggtgat ctgcccagac aagcagttac caaatggtgg agccagaact      360

cacctccttt aagaaggtga ttgtcctaca aactcatttg atggtgaggt ctggaatgta      420

aataatgtaa tgttcggcta accttctcct tctctccctc ccttcccctt ttcttttcag      480

ctctgaagat tcatttgaac ctgcttaatt acaaatccag tttctaatat gctatacaat      540

ttatgcacgc agaaagaaat agcaatgtac acatcacctt ctttatatct tactttaaat      600

gttttatgca tgttttcaaa aattggaaat atcctagata gctgagcaat aaatcttcaa      660

taagtatttt gatcagaata ataaatataa ttttaagaac aatagttgat catatgccaa      720

accctctgta cttctcatta cttggatgca gttactcatc tttggtctat cacaacataa      780

gtgacatact ttccttttgg taaagcaaag aggcctaatt gaagtctgtc actgtgccca      840

atgcttagca attctcaccc ccaaccctgt ggctacttct gcttttgtta cttttactaa      900

aaataaaaaa ctaaaaaaaa aaaaaaaaat tgctgccaga cattgccagt gttacatgaa      960

gtggtttcta ggtagcctaa atgcctgcaa gcacgtgcgt atttttcatc atctaaagag     1020

gcagtgggta tcttagaagg ttcttgcaga agcaggctcc tcaactaagg gtcgagagga     1080

aagtgactag gaaaggcctc caaagcagag cagtaggagg tggtgatgaa ggtcagggaa     1140

taataggaag aaactgagag gggagtgagg atctcagacg tgctggtccc acagggagct     1200

ctagagcaga gatcacatct tacagtttgt cttggtgatg tgcacagctt gttgctggct     1260

ccacaggact gtatgctagg atgaaagccc agatactttg gggtgcaggt tatggttatg     1320

gggtgcaagt tatggttatt gg                                              1342


<210>  54
<211>  3944
<212>  DNA
<213>  Homo sapiens

<400>  54
ggctctcact ccatgaggta tttcttcaca tccgtgtccc ggcccggccg cggggagccc       60

cgcttcatcg cagtgggcta cgtggacgac acgcagttcg tgcggttcga cagcgacgcc      120

gcgagccaga ggatggagcc gcgggcgccg tggatagagc aggagggtcc ggagtattgg      180

gacggggaga cacggaaagt gaaggcccac tcacagactc accgagtgga cctggggacc      240

ctgcgcggct actacaacca gagcgaggcc ggtgagtgac cccggcccgg ggcgcaggtc      300

acgacctctc atcccccacg gacgggccag gtcgcccaca gtctccgggt ccgagatccg      360

ccccgaagcc gcgggacccc gagacccttg ccccgggaga ggcccaggcg cctttacccg      420

gtttcatttt cagtttaggc caaaaatccc cccaggttgg tcggggcggg gcggggctcg      480

ggggaccggg ctgaccgcgg ggtccgggcc aggttctcac accgtccaga ggatgtatgg      540

ctgcgacgtg gggtcggact ggcgcttcct ccgcgggtac caccagtacg cctacgacgg      600

caaggattac atcgccctga aagaggacct gcgctcttgg accgcggcgg acatggcagc      660

tcagaccacc aagcacaagt gggaggcggc ccatgtggcg gagcagttga gagcctacct      720

ggagggcacg tgcgtggagt ggctccgcag atacctggag aacgggaagg agacgctgca      780

gcgcacgggt accaggggcc acggggcgcc tccctgatcg cctgtagatc tcccgggctg      840

gcctcccaca aggaggggag acaattggga ccaacactag aatatcgccc tccctctggt      900

cctgagggag aggaatcctc ctgggtttcc agatcctgta ccagagagtg actctgaggt      960

tccgccctgc tctctgacac aattaaggga taaaatctct gaaggaatga cgggaagacg     1020

atccctcgaa tactgatgag tggttccctt tgacacacac aggcagcagc cttgggcccg     1080

tgacttttcc tctcaggcct tgttctctgc ttcacactca atgtgtgtgg gggtctgagt     1140

ccagcacttc tgagtccttc agcctccact caggtcagga ccagaagtcg ctgttccctc     1200

ttcagggact agaattttcc acggaatagg agattatccc aggtgcctgt gtccaggctg     1260

gtgtctgggt tctgtgctcc cttccccatc ccaggtgtcc tgtccattct caagatagcc     1320

acatgtgtgc tggaggagtg tcccatgaca gatgcaaaat gcctgaatga tctgactctt     1380

cctgacagac gcccccaaaa cgcatatgac tcaccacgct gtctctgacc atgaagccac     1440

cctgaggtgc tgggccctga gcttctaccc tgcggagatc acactgacct ggcagcggga     1500

tggggaggac cagacccagg acacggagct cgtggagacc aggcctgcag gggatggaac     1560

cttccagaag tgggcggctg tggtggtgcc ttctggacag gagcagagat acacctgcca     1620

tgtgcagcat gagggtttgc ccaagcccct caccctgaga tggggtaagg agggagacgg     1680

gggtgtcatg tcttttaggg aaagcaggag cctctctgac ctttagcagg gtcagggccc     1740

ctcaccttcc cctcttttcc cagagccgtc ttcccagccc accatcccca tcgtgggcat     1800

cattgctggc ctggttctct ttggagctgt gatcactgga gctgtggtcg ctgctgtgat     1860

gtggaggagg aagagctcag gtggggaagg ggtgaagggt gggtctgaga tttcttgtct     1920

cactgagggt tccaagaccc aggtagaagt gtgccctgcc tcgttactgg gaagcaccac     1980

ccacaattat gggcctaccc agcctgggcc ctgtgtgcca gcacttactc ttttgtaaag     2040

cacctgttaa aatgaaggac agatttatca ccttgattac agcggtgatg ggacctgatc     2100

ccagcagtca caagtcacag gggaaggtcc ctgaggacct tcaggagggc ggttggtcca     2160

ggacccacac ctgctttctt catgtttcct gatcccgccc tgggtctgca gtcacacatt     2220

tctggaaact tctctgaggt ccaagacttg gaggttcctc taggacctta aggccctgac     2280

tcctttctgg tatctcacag gacattttct tcccacagat agaaaaggag ggagctactc     2340

tcaggctgca agtaagtatg aaggaggctg atgcctgagg tccttgggat attgtgtttg     2400

ggagcccatg ggggagctca cccaccccac aattcctcct ctagccacat cttctgtggg     2460

atctgaccag gttctgtttt tgttctaccc caggcagtga cagtgcccag ggctctgatg     2520

tgtctctcac agcttgtaaa ggtgagagcc tggagggcct gatgtgtgtt gggtgttggg     2580

cggaacagtg gacacagctg tgctatgggg tttctttcca ttggatgtat tgagcatgcg     2640

atgggctgtt taaagtgtga cccctcactg tgacagatac gaatttgttc atgaatattt     2700

ttttctatag tgtgagacag ctgccttgtg tgggactgag aggcaagagt tgttcctgcc     2760

cttccctttg tgacttgaag aaccctgact ttgtttctgc aaaggcacct gcatgtgtct     2820

gtgttcgtgt aggcataatg tgaggaggtg gggagaccac cccaccccca tgtccaccat     2880

gaccctcttc ccacgctgac ctgtgctccc tccccaatca tctttcctgt tccagagagg     2940

tggggctgag gtgtctccat ctctgtctca acttcatggt gcactgagct gtaacttctt     3000

ccttccctat taaaattaga acctgagtat aaatttactt tctcaaattc ttgccatgag     3060

aggttgatga gttaattaaa ggagaagatt cctaaaattt gagagacaaa ataaatggaa     3120

cacatgagaa ccttccagag tccacgtgtt gcttatgctg atttgttgca ggggaggaga     3180

gtagatgggg ctgtgcccag tttctgttcc ggccactatg ggctttatgt ggtcactgct     3240

tggctgggtc atctttgctg ctccattgtc cttggccctt cagtagaacc ttgtcccact     3300

aagacctgtg atcacaggga gttggatgtc acctagggtg gtccctgcat acaaatctcc     3360

ttgcggtatc aagagacaaa ttttcagacc tgtctaggtc ttgccttcct cccagggctt     3420

tttcctcaat tgtattttca atttttctcc aatcttttta aaggaaccag attgtgacat     3480

ttgcagagag gagtggtccc atagtttctc atcatgatta actttctgtt ggaactcctg     3540

ttctgccctc ctactcttct tcctgctctg aattgtagta atcctagtgc tggctccaat     3600

ccaaactcat agatttataa agcagagtct aatttagatt catatgtggt tggaaaattg     3660

tacccataag gctagggtta ttgttcctga agagaaatat atggttttgt gctgaagtgt     3720

gcaggagggt tggtgtggga ggagggagga cacacaagca gccctggtga gaaaagcact     3780

ggcggcgtgg atgtccatgt gaacttatgt tctttagctg ccacaaaaca gcatttgccc     3840

tgtggctaca ttaataaagg tatgggcttt agaataggga gatgctctac agtggtcatt     3900

cattcaactg acatttgttg tctgctaggg atatgactgc tttt                      3944


<210>  55
<211>  24
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  5' end primer

<400>  55
cagctccaaa gagaaccagg ccag                                              24


<210>  56
<211>  24
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  3' end primer

<400>  56
taccctgcgg agatcacact gacc                                              24


<210>  57
<211>  24
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Probe primer

<400>  57
ttctgatgct ccttccttcc gtgc                                              24


<210>  58
<211>  24
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Probe primer

<400>  58
ttctctgtgc tcagtgttcc ctgc                                              24


<210>  59
<211>  362
<212>  PRT
<213>  Homo sapiens

<400>  59

Met Ala Pro Arg Thr Leu Val Leu Leu Leu Ser Gly Ala Leu Ala Leu 
1               5                   10                  15      


Thr Gln Thr Trp Ala Gly Ser His Ser Met Arg Tyr Phe Phe Thr Ser 
            20                  25                  30          


Val Ser Arg Pro Gly Arg Gly Glu Pro Arg Phe Ile Ala Val Gly Tyr 
        35                  40                  45              


Val Asp Asp Thr Gln Phe Val Arg Phe Asp Ser Asp Ala Ala Ser Gln 
    50                  55                  60                  


Arg Met Glu Pro Arg Ala Pro Trp Ile Glu Gln Glu Gly Pro Glu Tyr 
65                  70                  75                  80  


Trp Asp Gly Glu Thr Arg Lys Val Lys Ala His Ser Gln Thr His Arg 
                85                  90                  95      


Val Asp Leu Gly Thr Leu Arg Gly Tyr Tyr Asn Gln Ser Glu Ala Gly 
            100                 105                 110         


Ser His Thr Val Gln Arg Met Tyr Gly Cys Asp Val Gly Ser Asp Trp 
        115                 120                 125             


Arg Phe Leu Arg Gly Tyr His Gln Tyr Ala Tyr Asp Gly Lys Asp Tyr 
    130                 135                 140                 


Ile Ala Leu Lys Glu Asp Leu Arg Ser Trp Thr Ala Ala Asp Met Ala 
145                 150                 155                 160 


Ala Gln Thr Thr Lys His Lys Trp Glu Ala Ala His Val Ala Glu Gln 
                165                 170                 175     


Leu Arg Ala Tyr Leu Glu Gly Thr Cys Val Glu Trp Leu Arg Arg Tyr 
            180                 185                 190         


Leu Glu Asn Gly Lys Glu Thr Leu Gln Arg Thr Asp Ala Pro Lys Thr 
        195                 200                 205             


His Met Thr His His Ala Val Ser Asp His Glu Ala Thr Leu Arg Cys 
    210                 215                 220                 


Trp Ala Leu Ser Phe Tyr Pro Ala Glu Ile Thr Leu Thr Trp Gln Arg 
225                 230                 235                 240 


Asp Gly Glu Asp Gln Thr Gln Asp Thr Glu Leu Val Glu Thr Arg Pro 
                245                 250                 255     


Ala Gly Asp Gly Thr Phe Gln Lys Trp Ala Ala Val Val Val Pro Ser 
            260                 265                 270         


Gly Gln Glu Gln Arg Tyr Thr Cys His Val Gln His Glu Gly Leu Pro 
        275                 280                 285             


Lys Pro Leu Thr Leu Arg Trp Glu Pro Ser Ser Gln Pro Thr Ile Pro 
    290                 295                 300                 


Ile Val Gly Ile Ile Ala Gly Leu Val Leu Phe Gly Ala Val Ile Thr 
305                 310                 315                 320 


Gly Ala Val Val Ala Ala Val Met Trp Arg Arg Lys Ser Ser Asp Arg 
                325                 330                 335     


Lys Gly Gly Ser Tyr Ser Gln Ala Ala Ser Ser Asp Ser Ala Gln Gly 
            340                 345                 350         


Ser Asp Val Ser Leu Thr Ala Cys Lys Val 
        355                 360         


<210>  60
<211>  1409
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  5' arm

<400>  60
gcatttccta gtacagttca acacagtgtt tagtataatt taatattaac atttcaggtc       60

tttaatgtat taaatgagtt tttcttttta attagatgaa gtatcttaac tcacaccttt      120

atacataaaa attattctta tatttcagtt acaaaaaggg atagcaaaat aacataaatg      180

attatgattc ttaaacatta ctggatcaaa atactatatg ctgggtagac actgtaggat      240

tgggtctctg tttattatct cattaatgtc cgtggagact attttatttt tttctagttt      300

agacacagcc tccacactag agattgttaa aggtttttaa aaatatgttc aagaaatcca      360

gaagttatgt tgttctcctt ggggaagcca aggccaaagc cacttcaact gcaagcatgg      420

ccatttctcc atgtcctgat gccccatgcc ctcttcctac ccttcctcac tcgagctgct      480

tgcggtggtg tctccctgtg ctcacagcct gcctctgtcc tggcttttgg ccaggggttt      540

aacttctcta ctgggtccac cgctgatgta atatacattc tgagtaaaac tatggcagcc      600

tttgtcttcc gagccgataa gcagaaaccc caagggaatg catctcaagg tttatctcct      660

catccagaaa aaataattta ttcgggtatt cacttcactt ggtcacttag tttaccaatg      720

gccctgttct aagaaagtac tactaagaga atggacagga aacccagcta agccattgtt      780

cttccccaaa acccatggac agaacaaaga aaattaccta aatttttcaa gggtacccga      840

ttaagttctc catccaaagc tctaaaagga gaaacctgct agaagcaagg tcagaaatcc      900

tctcagttgc ctttaggaca ggagggtctt tttacacacg gaatcctgaa actgcctttg      960

tatttctggg ctgagattat aaactaaggg ttgagttctg ccagttaatg ctcttaattg     1020

tcctggcttt agttttcaag aatgcaaact tcaggtccta agtccttttc tgagtgggat     1080

attgtcagca attgaataaa tgaaggcggt cccaggctga acgaccagat acaccaaact     1140

caagagcaca ccctagatag tagggcacca agggtccagc ccaggctgtt tgaaatatca     1200

cgggacttta taagaacatg aaactgaaaa tgggaaagtc cctttgtaac ctagttcagc     1260

attaacagct aggagactgg tgacgacctc cggatctgag tccggattgg ctgtgagttc     1320

aggaactata taagagcgcg cgccctggct ggctctcatt tcagtggctg ctactcggcg     1380

cttcagtcgc ggtcgcttca gtcgtcagc                                       1409


<210>  61
<211>  476
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Protein sequence of humanized C57

<400>  61

Met Ala Val Met Ala Pro Arg Thr Leu Val Leu Leu Leu Ser Gly Ala 
1               5                   10                  15      


Leu Ala Leu Thr Gln Thr Trp Ala Ile Gln Arg Thr Pro Lys Ile Gln 
            20                  25                  30          


Val Tyr Ser Arg His Pro Ala Glu Asn Gly Lys Ser Asn Phe Leu Asn 
        35                  40                  45              


Cys Tyr Val Ser Gly Phe His Pro Ser Asp Ile Glu Val Asp Leu Leu 
    50                  55                  60                  


Lys Asn Gly Glu Arg Ile Glu Lys Val Glu His Ser Asp Leu Ser Phe 
65                  70                  75                  80  


Ser Lys Asp Trp Ser Phe Tyr Leu Leu Tyr Tyr Thr Glu Phe Thr Pro 
                85                  90                  95      


Thr Glu Lys Asp Glu Tyr Ala Cys Arg Val Asn His Val Thr Leu Ser 
            100                 105                 110         


Gln Pro Lys Ile Val Lys Trp Asp Arg Asp Met Gly Gly Gly Gly Ser 
        115                 120                 125             


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Ser His Ser Met Arg 
    130                 135                 140                 


Tyr Phe Phe Thr Ser Val Ser Arg Pro Gly Arg Gly Glu Pro Arg Phe 
145                 150                 155                 160 


Ile Ala Val Gly Tyr Val Asp Asp Thr Gln Phe Val Arg Phe Asp Ser 
                165                 170                 175     


Asp Ala Ala Ser Gln Arg Met Glu Pro Arg Ala Pro Trp Ile Glu Gln 
            180                 185                 190         


Glu Gly Pro Glu Tyr Trp Asp Gly Glu Thr Arg Lys Val Lys Ala His 
        195                 200                 205             


Ser Gln Thr His Arg Val Asp Leu Gly Thr Leu Arg Gly Tyr Tyr Asn 
    210                 215                 220                 


Gln Ser Glu Ala Gly Ser His Thr Val Gln Arg Met Tyr Gly Cys Asp 
225                 230                 235                 240 


Val Gly Ser Asp Trp Arg Phe Leu Arg Gly Tyr His Gln Tyr Ala Tyr 
                245                 250                 255     


Asp Gly Lys Asp Tyr Ile Ala Leu Lys Glu Asp Leu Arg Ser Trp Thr 
            260                 265                 270         


Ala Ala Asp Met Ala Ala Gln Thr Thr Lys His Lys Trp Glu Ala Ala 
        275                 280                 285             


His Val Ala Glu Gln Leu Arg Ala Tyr Leu Glu Gly Thr Cys Val Glu 
    290                 295                 300                 


Trp Leu Arg Arg Tyr Leu Glu Asn Gly Lys Glu Thr Leu Gln Arg Thr 
305                 310                 315                 320 


Asp Ser Pro Lys Ala His Val Thr His His Pro Arg Ser Lys Gly Glu 
                325                 330                 335     


Val Thr Leu Arg Cys Trp Ala Leu Gly Phe Tyr Pro Ala Asp Ile Thr 
            340                 345                 350         


Leu Thr Trp Gln Leu Asn Gly Glu Glu Leu Thr Gln Asp Met Glu Leu 
        355                 360                 365             


Val Glu Thr Arg Pro Ala Gly Asp Gly Thr Phe Gln Lys Trp Ala Ser 
    370                 375                 380                 


Val Val Val Pro Leu Gly Lys Glu Gln Asn Tyr Thr Cys Arg Val Tyr 
385                 390                 395                 400 


His Glu Gly Leu Pro Glu Pro Leu Thr Leu Arg Trp Glu Pro Pro Pro 
                405                 410                 415     


Ser Thr Asp Ser Tyr Met Val Ile Val Ala Val Leu Gly Val Leu Gly 
            420                 425                 430         


Ala Met Ala Ile Ile Gly Ala Val Val Ala Phe Val Met Lys Arg Arg 
        435                 440                 445             


Arg Asn Thr Gly Gly Lys Gly Gly Asp Tyr Ala Leu Ala Pro Gly Ser 
    450                 455                 460                 


Gln Ser Ser Glu Met Ser Leu Arg Asp Cys Lys Ala 
465                 470                 475     


<210>  62
<211>  479
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Protein sequence of humanized NDG

<400>  62

Met Ala Val Met Ala Pro Arg Thr Leu Val Leu Leu Leu Ser Gly Ala 
1               5                   10                  15      


Leu Ala Leu Thr Gln Thr Trp Ala Ile Gln Arg Thr Pro Lys Ile Gln 
            20                  25                  30          


Val Tyr Ser Arg His Pro Ala Glu Asn Gly Lys Ser Asn Phe Leu Asn 
        35                  40                  45              


Cys Tyr Val Ser Gly Phe His Pro Ser Asp Ile Glu Val Asp Leu Leu 
    50                  55                  60                  


Lys Asn Gly Glu Arg Ile Glu Lys Val Glu His Ser Asp Leu Ser Phe 
65                  70                  75                  80  


Ser Lys Asp Trp Ser Phe Tyr Leu Leu Tyr Tyr Thr Glu Phe Thr Pro 
                85                  90                  95      


Thr Glu Lys Asp Glu Tyr Ala Cys Arg Val Asn His Val Thr Leu Ser 
            100                 105                 110         


Gln Pro Lys Ile Val Lys Trp Asp Arg Asp Met Gly Gly Gly Gly Ser 
        115                 120                 125             


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Ser His Ser Met Arg 
    130                 135                 140                 


Tyr Phe Phe Thr Ser Val Ser Arg Pro Gly Arg Gly Glu Pro Arg Phe 
145                 150                 155                 160 


Ile Ala Val Gly Tyr Val Asp Asp Thr Gln Phe Val Arg Phe Asp Ser 
                165                 170                 175     


Asp Ala Ala Ser Gln Arg Met Glu Pro Arg Ala Pro Trp Ile Glu Gln 
            180                 185                 190         


Glu Gly Pro Glu Tyr Trp Asp Gly Glu Thr Arg Lys Val Lys Ala His 
        195                 200                 205             


Ser Gln Thr His Arg Val Asp Leu Gly Thr Leu Arg Gly Tyr Tyr Asn 
    210                 215                 220                 


Gln Ser Glu Ala Gly Ser His Thr Val Gln Arg Met Tyr Gly Cys Asp 
225                 230                 235                 240 


Val Gly Ser Asp Trp Arg Phe Leu Arg Gly Tyr His Gln Tyr Ala Tyr 
                245                 250                 255     


Asp Gly Lys Asp Tyr Ile Ala Leu Lys Glu Asp Leu Arg Ser Trp Thr 
            260                 265                 270         


Ala Ala Asp Met Ala Ala Gln Thr Thr Lys His Lys Trp Glu Ala Ala 
        275                 280                 285             


His Val Ala Glu Gln Leu Arg Ala Tyr Leu Glu Gly Thr Cys Val Glu 
    290                 295                 300                 


Trp Leu Arg Arg Tyr Leu Glu Asn Gly Lys Glu Thr Leu Gln Arg Thr 
305                 310                 315                 320 


Asp Ala Pro Lys Thr His Met Thr His His Ala Val Ser Asp His Glu 
                325                 330                 335     


Ala Thr Leu Arg Cys Trp Ala Leu Ser Phe Tyr Pro Ala Glu Ile Thr 
            340                 345                 350         


Leu Thr Trp Gln Arg Asp Gly Glu Asp Gln Thr Gln Asp Thr Glu Leu 
        355                 360                 365             


Val Glu Thr Arg Pro Ala Gly Asp Gly Thr Phe Gln Lys Trp Ala Ala 
    370                 375                 380                 


Val Val Val Pro Ser Gly Gln Glu Gln Arg Tyr Thr Cys His Val Gln 
385                 390                 395                 400 


His Glu Gly Leu Pro Lys Pro Leu Thr Leu Arg Trp Glu Pro Ser Ser 
                405                 410                 415     


Gln Pro Thr Ile Pro Ile Val Gly Ile Ile Ala Gly Leu Val Leu Phe 
            420                 425                 430         


Gly Ala Val Ile Thr Gly Ala Val Val Ala Ala Val Met Trp Arg Arg 
        435                 440                 445             


Lys Ser Ser Asp Arg Lys Gly Gly Ser Tyr Ser Gln Ala Ala Ser Ser 
    450                 455                 460                 


Asp Ser Ala Gln Gly Ser Asp Val Ser Leu Thr Ala Cys Lys Val 
465                 470                 475                 


<210>  63
<211>  337
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human B2M and HLA-A2.1 protein signal peptide, Alpha-1and Alpha-2
       regions

<400>  63

Met Ser Arg Ser Val Ala Leu Ala Val Leu Ala Leu Leu Ser Leu Ser 
1               5                   10                  15      


Gly Leu Glu Ala Ile Gln Arg Thr Pro Lys Ile Gln Val Tyr Ser Arg 
            20                  25                  30          


His Pro Ala Glu Asn Gly Lys Ser Asn Phe Leu Asn Cys Tyr Val Ser 
        35                  40                  45              


Gly Phe His Pro Ser Asp Ile Glu Val Asp Leu Leu Lys Asn Gly Glu 
    50                  55                  60                  


Arg Ile Glu Lys Val Glu His Ser Asp Leu Ser Phe Ser Lys Asp Trp 
65                  70                  75                  80  


Ser Phe Tyr Leu Leu Tyr Tyr Thr Glu Phe Thr Pro Thr Glu Lys Asp 
                85                  90                  95      


Glu Tyr Ala Cys Arg Val Asn His Val Thr Leu Ser Gln Pro Lys Ile 
            100                 105                 110         


Val Lys Trp Asp Arg Asp Met Gly Gly Gly Gly Ser Gly Gly Gly Gly 
        115                 120                 125             


Ser Gly Gly Gly Gly Ser Met Ala Pro Arg Thr Leu Val Leu Leu Leu 
    130                 135                 140                 


Ser Gly Ala Leu Ala Leu Thr Gln Thr Trp Ala Gly Ser His Ser Met 
145                 150                 155                 160 


Arg Tyr Phe Phe Thr Ser Val Ser Arg Pro Gly Arg Gly Glu Pro Arg 
                165                 170                 175     


Phe Ile Ala Val Gly Tyr Val Asp Asp Thr Gln Phe Val Arg Phe Asp 
            180                 185                 190         


Ser Asp Ala Ala Ser Gln Arg Met Glu Pro Arg Ala Pro Trp Ile Glu 
        195                 200                 205             


Gln Glu Gly Pro Glu Tyr Trp Asp Gly Glu Thr Arg Lys Val Lys Ala 
    210                 215                 220                 


His Ser Gln Thr His Arg Val Asp Leu Gly Thr Leu Arg Gly Tyr Tyr 
225                 230                 235                 240 


Asn Gln Ser Glu Ala Gly Ser His Thr Val Gln Arg Met Tyr Gly Cys 
                245                 250                 255     


Asp Val Gly Ser Asp Trp Arg Phe Leu Arg Gly Tyr His Gln Tyr Ala 
            260                 265                 270         


Tyr Asp Gly Lys Asp Tyr Ile Ala Leu Lys Glu Asp Leu Arg Ser Trp 
        275                 280                 285             


Thr Ala Ala Asp Met Ala Ala Gln Thr Thr Lys His Lys Trp Glu Ala 
    290                 295                 300                 


Ala His Val Ala Glu Gln Leu Arg Ala Tyr Leu Glu Gly Thr Cys Val 
305                 310                 315                 320 


Glu Trp Leu Arg Arg Tyr Leu Glu Asn Gly Lys Glu Thr Leu Gln Arg 
                325                 330                 335     


Thr 
    


<210>  64
<211>  358
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  The signal peptide, Alpha-1 and Alpha-2 regions of human HLA-A2.1
       protein and Alpha-3, connecting peptide, transmembrane region and
       intracellular region of mouse H2-D1

<400>  64

Met Ala Pro Arg Thr Leu Val Leu Leu Leu Ser Gly Ala Leu Ala Leu 
1               5                   10                  15      


Thr Gln Thr Trp Ala Gly Ser His Ser Met Arg Tyr Phe Phe Thr Ser 
            20                  25                  30          


Val Ser Arg Pro Gly Arg Gly Glu Pro Arg Phe Ile Ala Val Gly Tyr 
        35                  40                  45              


Val Asp Asp Thr Gln Phe Val Arg Phe Asp Ser Asp Ala Ala Ser Gln 
    50                  55                  60                  


Arg Met Glu Pro Arg Ala Pro Trp Ile Glu Gln Glu Gly Pro Glu Tyr 
65                  70                  75                  80  


Trp Asp Gly Glu Thr Arg Lys Val Lys Ala His Ser Gln Thr His Arg 
                85                  90                  95      


Val Asp Leu Gly Thr Leu Arg Gly Tyr Tyr Asn Gln Ser Glu Ala Gly 
            100                 105                 110         


Ser His Thr Val Gln Arg Met Tyr Gly Cys Asp Val Gly Ser Asp Trp 
        115                 120                 125             


Arg Phe Leu Arg Gly Tyr His Gln Tyr Ala Tyr Asp Gly Lys Asp Tyr 
    130                 135                 140                 


Ile Ala Leu Lys Glu Asp Leu Arg Ser Trp Thr Ala Ala Asp Met Ala 
145                 150                 155                 160 


Ala Gln Thr Thr Lys His Lys Trp Glu Ala Ala His Val Ala Glu Gln 
                165                 170                 175     


Leu Arg Ala Tyr Leu Glu Gly Thr Cys Val Glu Trp Leu Arg Arg Tyr 
            180                 185                 190         


Leu Glu Asn Gly Lys Glu Thr Leu Gln Arg Thr Ser Pro Lys Ala His 
        195                 200                 205             


Val Thr His His Pro Arg Ser Lys Gly Glu Val Thr Leu Arg Cys Trp 
    210                 215                 220                 


Ala Leu Gly Phe Tyr Pro Ala Asp Ile Thr Leu Thr Trp Gln Leu Asn 
225                 230                 235                 240 


Gly Glu Glu Leu Thr Gln Asp Met Glu Leu Val Glu Thr Arg Pro Ala 
                245                 250                 255     


Gly Asp Gly Thr Phe Gln Lys Trp Ala Ser Val Val Val Pro Leu Gly 
            260                 265                 270         


Lys Glu Gln Asn Tyr Thr Cys Arg Val Tyr His Glu Gly Leu Pro Glu 
        275                 280                 285             


Pro Leu Thr Leu Arg Trp Glu Pro Pro Pro Ser Thr Asp Ser Tyr Met 
    290                 295                 300                 


Val Ile Val Ala Val Leu Gly Val Leu Gly Ala Met Ala Ile Ile Gly 
305                 310                 315                 320 


Ala Val Val Ala Phe Val Met Lys Arg Arg Arg Asn Thr Gly Gly Lys 
                325                 330                 335     


Gly Gly Asp Tyr Ala Leu Ala Pro Gly Ser Gln Ser Ser Glu Met Ser 
            340                 345                 350         


Leu Arg Asp Cys Lys Ala 
        355             


<210>  65
<211>  3690
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  the BNDG-A fragment

<400>  65
atggccgtca tggcgccccg aaccctcgtc ctgctactct cgggggctct ggccctgacc       60

cagacctggg cgatccagcg tactccaaag attcaggttt actcacgtca tccagcagag      120

aatggaaagt caaatttcct gaattgctat gtgtctgggt ttcatccatc cgacattgaa      180

gttgacttac tgaagaatgg agagagaatt gaaaaagtgg agcattcaga cttgtctttc      240

agcaaggact ggtctttcta tctcttgtac tacactgaat tcacccccac tgaaaaagat      300

gagtatgcct gccgtgtgaa ccatgtgact ttgtcacagc ccaagatagt taagtgggat      360

cgagacatgg gaggtggcgg atccggcgga ggcggctcgg gtggcggcgg ctctggctct      420

cactccatga ggtatttctt cacatccgtg tcccggcccg gccgcgggga gccccgcttc      480

atcgcagtgg gctacgtgga cgacacgcag ttcgtgcggt tcgacagcga cgccgcgagc      540

cagaggatgg agccgcgggc gccgtggata gagcaggagg gtccggagta ttgggacggg      600

gagacacgga aagtgaaggc ccactcacag actcaccgag tggacctggg gaccctgcgc      660

ggctactaca accagagcga ggccggtgag tgaccccggc ccggggcgca ggtcacgacc      720

tctcatcccc cacggacggg ccaggtcgcc cacagtctcc gggtccgaga tccgccccga      780

agccgcggga ccccgagacc cttgccccgg gagaggccca ggcgccttta cccggtttca      840

ttttcagttt aggccaaaaa tccccccagg ttggtcgggg cggggcgggg ctcgggggac      900

cgggctgacc gcggggtccg ggccaggttc tcacaccgtc cagaggatgt atggctgcga      960

cgtggggtcg gactggcgct tcctccgcgg gtaccaccag tacgcctacg acggcaagga     1020

ttacatcgcc ctgaaagagg acctgcgctc ttggaccgcg gcggacatgg cagctcagac     1080

caccaagcac aagtgggagg cggcccatgt ggcggagcag ttgagagcct acctggaggg     1140

cacgtgcgtg gagtggctcc gcagatacct ggagaacggg aaggagacgc tgcagcgcac     1200

gggtaccagg ggccacgggg cgcctccctg atcgcctgta gatctcccgg gctggcctcc     1260

cacaaggagg ggagacaatt gggaccaaca ctagaatatc gccctccctc tggtcctgag     1320

ggagaggaat cctcctgggt ttccagatcc tgtaccagag agtgactctg aggttccgcc     1380

ctgctctctg acacaattaa gggataaaat ctctgaagga atgacgggaa gacgatccct     1440

cgaatactga tgagtggttc cctttgacac acacaggcag cagccttggg cccgtgactt     1500

ttcctctcag gccttgttct ctgcttcaca ctcaatgtgt gtgggggtct gagtccagca     1560

cttctgagtc cttcagcctc cactcaggtc aggaccagaa gtcgctgttc cctcttcagg     1620

gactagaatt ttccacggaa taggagatta tcccaggtgc ctgtgtccag gctggtgtct     1680

gggttctgtg ctcccttccc catcccaggt gtcctgtcca ttctcaagat agccacatgt     1740

gtgctggagg agtgtcccat gacagatgca aaatgcctga atgatctgac tcttcctgac     1800

agacgccccc aaaacgcata tgactcacca cgctgtctct gaccatgaag ccaccctgag     1860

gtgctgggcc ctgagcttct accctgcgga gatcacactg acctggcagc gggatgggga     1920

ggaccagacc caggacacgg agctcgtgga gaccaggcct gcaggggatg gaaccttcca     1980

gaagtgggcg gctgtggtgg tgccttctgg acaggagcag agatacacct gccatgtgca     2040

gcatgagggt ttgcccaagc ccctcaccct gagatggggt aaggagggag acgggggtgt     2100

catgtctttt agggaaagca ggagcctctc tgacctttag cagggtcagg gcccctcacc     2160

ttcccctctt ttcccagagc cgtcttccca gcccaccatc cccatcgtgg gcatcattgc     2220

tggcctggtt ctctttggag ctgtgatcac tggagctgtg gtcgctgctg tgatgtggag     2280

gaggaagagc tcaggtgggg aaggggtgaa gggtgggtct gagatttctt gtctcactga     2340

gggttccaag acccaggtag aagtgtgccc tgcctcgtta ctgggaagca ccacccacaa     2400

ttatgggcct acccagcctg ggccctgtgt gccagcactt actcttttgt aaagcacctg     2460

ttaaaatgaa ggacagattt atcaccttga ttacagcggt gatgggacct gatcccagca     2520

gtcacaagtc acaggggaag gtccctgagg accttcagga gggcggttgg tccaggaccc     2580

acacctgctt tcttcatgtt tcctgatccc gccctgggtc tgcagtcaca catttctgga     2640

aacttctctg aggtccaaga cttggaggtt cctctaggac cttaaggccc tgactccttt     2700

ctggtatctc acaggacatt ttcttcccac agatagaaaa ggagggagct actctcaggc     2760

tgcaagtaag tatgaaggag gctgatgcct gaggtccttg ggatattgtg tttgggagcc     2820

catgggggag ctcacccacc ccacaattcc tcctctagcc acatcttctg tgggatctga     2880

ccaggttctg tttttgttct accccaggca gtgacagtgc ccagggctct gatgtgtctc     2940

tcacagcttg taaaggtgag agcctggagg gcctgatgtg tgttgggtgt tgggcggaac     3000

agtggacaca gctgtgctat ggggtttctt tccattggat gtattgagca tgcgatgggc     3060

tgtttaaagt gtgacccctc actgtgacag atacgaattt gttcatgaat atttttttct     3120

atagtgtgag acagctgcct tgtgtgggac tgagaggcaa gagttgttcc tgcccttccc     3180

tttgtgactt gaagaaccct gactttgttt ctgcaaaggc acctgcatgt gtctgtgttc     3240

gtgtaggcat aatgtgagga ggtggggaga ccaccccacc cccatgtcca ccatgaccct     3300

cttcccacgc tgacctgtgc tccctcccca atcatctttc ctgttccaga gaggtggggc     3360

tgaggtgtct ccatctctgt ctcaacttca tggtgcactg agctgtaact tcttccttcc     3420

ctattaaaat tagaacctga gtataaattt actttctcaa attcttgcca tgagaggttg     3480

atgagttaat taaaggagaa gattcctaaa atttgagaga caaaataaat ggaacacatg     3540

agaaccttcc agagtccacg tgttgcttat gctgatttgt tgcaggggag gagagtagat     3600

ggggctgtgc ccagtttctg ttccggccac tatgggcttt atgtggtcac tgcttggctg     3660

ggtcatcttt gctgctccat tgtccttggc                                      3690


<210>  66
<211>  119
<212>  PRT
<213>  Rattus norvegicus

<400>  66

Met Ala Arg Ser Val Thr Val Ile Phe Leu Val Leu Val Ser Leu Ala 
1               5                   10                  15      


Val Val Leu Ala Ile Gln Lys Thr Pro Gln Ile Gln Val Tyr Ser Arg 
            20                  25                  30          


His Pro Pro Glu Asn Gly Lys Pro Asn Phe Leu Asn Cys Tyr Val Ser 
        35                  40                  45              


Gln Phe His Pro Pro Gln Ile Glu Ile Glu Leu Leu Lys Asn Gly Lys 
    50                  55                  60                  


Lys Ile Pro Asn Ile Glu Met Ser Asp Leu Ser Phe Ser Lys Asp Trp 
65                  70                  75                  80  


Ser Phe Tyr Ile Leu Ala His Thr Glu Phe Thr Pro Thr Glu Thr Asp 
                85                  90                  95      


Val Tyr Ala Cys Arg Val Lys His Val Thr Leu Lys Glu Pro Lys Thr 
            100                 105                 110         


Val Thr Trp Asp Arg Asp Met 
        115                 


<210>  67
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  The linker polypeptide sequence

<400>  67

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
1               5                   10                  15  


<210>  68
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  The linker polypeptide sequence

<400>  68

Gly Gly Gly Gly Ser 
1               5   


