                         SEQUENCE LISTING

<110>  Biocytogen JiangSu Co.,Ltd., Biocytogen PharmaceuticalsBeijingCo., Ltd.
 
<120>  GENETICALLY MODIFIED NON-HUMAN ANIMAL WITH HUMAN OR CHIMERIC 
       TNFSF9 AND/OR 4-1BB

<130>  1

<160>  59    

<170>  PatentIn version 3.5

<210>  1
<211>  1230
<212>  DNA
<213>  Mus musculus

<400>  1
ataaagcacg ggcactggcg ggagacgtgc actgaccgac cgtggtaatg gaccagcaca       60

cacttgatgt ggaggatacc gcggatgcca gacatccagc aggtacttcg tgcccctcgg      120

atgcggcgct cctcagagat accgggctcc tcgcggacgc tgcgctcctc tcagatactg      180

tgcgccccac aaatgccgcg ctccccacgg atgctgccta ccctgcggtt aatgttcggg      240

atcgcgaggc cgcgtggccg cctgcactga acttctgttc ccgccaccca aagctctatg      300

gcctagtcgc tttggttttg ctgcttctga tcgccgcctg tgttcctatc ttcacccgca      360

ccgagcctcg gccagcgctc acaatcacca cctcgcccaa cctgggtacc cgagagaata      420

atgcagacca ggtcacccct gtttcccaca ttggctgccc caacactaca caacagggct      480

ctcctgtgtt cgccaagcta ctggctaaaa accaagcatc gttgtgcaat acaactctga      540

actggcacag ccaagatgga gctgggagct catacctatc tcaaggtctg aggtacgaag      600

aagacaaaaa ggagttggtg gtagacagtc ccgggctcta ctacgtattt ttggaactga      660

agctcagtcc aacattcaca aacacaggcc acaaggtgca gggctgggtc tctcttgttt      720

tgcaagcaaa gcctcaggta gatgactttg acaacttggc cctgacagtg gaactgttcc      780

cttgctccat ggagaacaag ttagtggacc gttcctggag tcaactgttg ctcctgaagg      840

ctggccaccg cctcagtgtg ggtctgaggg cttatctgca tggagcccag gatgcataca      900

gagactggga gctgtcttat cccaacacca ccagctttgg actctttctt gtgaaacccg      960

acaacccatg ggaatgagaa ctatccttct tgtgactcct agttgctaag tcctcaagct     1020

gctatgtttt atggggtctg agcaggggtc ccttccatga ctttctcttg tctttaactg     1080

gacttggtat ttattctgag catagctcag acaagacttt atataattca ctagatagca     1140

ttagtaaact gctgggcagc tgctagataa aaaaaaattt ctaaatcaaa gtttatattt     1200

atattaatat ataaaaataa atgtgtttgt                                      1230


<210>  2
<211>  309
<212>  PRT
<213>  Mus musculus

<400>  2

Met Asp Gln His Thr Leu Asp Val Glu Asp Thr Ala Asp Ala Arg His 
1               5                   10                  15      


Pro Ala Gly Thr Ser Cys Pro Ser Asp Ala Ala Leu Leu Arg Asp Thr 
            20                  25                  30          


Gly Leu Leu Ala Asp Ala Ala Leu Leu Ser Asp Thr Val Arg Pro Thr 
        35                  40                  45              


Asn Ala Ala Leu Pro Thr Asp Ala Ala Tyr Pro Ala Val Asn Val Arg 
    50                  55                  60                  


Asp Arg Glu Ala Ala Trp Pro Pro Ala Leu Asn Phe Cys Ser Arg His 
65                  70                  75                  80  


Pro Lys Leu Tyr Gly Leu Val Ala Leu Val Leu Leu Leu Leu Ile Ala 
                85                  90                  95      


Ala Cys Val Pro Ile Phe Thr Arg Thr Glu Pro Arg Pro Ala Leu Thr 
            100                 105                 110         


Ile Thr Thr Ser Pro Asn Leu Gly Thr Arg Glu Asn Asn Ala Asp Gln 
        115                 120                 125             


Val Thr Pro Val Ser His Ile Gly Cys Pro Asn Thr Thr Gln Gln Gly 
    130                 135                 140                 


Ser Pro Val Phe Ala Lys Leu Leu Ala Lys Asn Gln Ala Ser Leu Cys 
145                 150                 155                 160 


Asn Thr Thr Leu Asn Trp His Ser Gln Asp Gly Ala Gly Ser Ser Tyr 
                165                 170                 175     


Leu Ser Gln Gly Leu Arg Tyr Glu Glu Asp Lys Lys Glu Leu Val Val 
            180                 185                 190         


Asp Ser Pro Gly Leu Tyr Tyr Val Phe Leu Glu Leu Lys Leu Ser Pro 
        195                 200                 205             


Thr Phe Thr Asn Thr Gly His Lys Val Gln Gly Trp Val Ser Leu Val 
    210                 215                 220                 


Leu Gln Ala Lys Pro Gln Val Asp Asp Phe Asp Asn Leu Ala Leu Thr 
225                 230                 235                 240 


Val Glu Leu Phe Pro Cys Ser Met Glu Asn Lys Leu Val Asp Arg Ser 
                245                 250                 255     


Trp Ser Gln Leu Leu Leu Leu Lys Ala Gly His Arg Leu Ser Val Gly 
            260                 265                 270         


Leu Arg Ala Tyr Leu His Gly Ala Gln Asp Ala Tyr Arg Asp Trp Glu 
        275                 280                 285             


Leu Ser Tyr Pro Asn Thr Thr Ser Phe Gly Leu Phe Leu Val Lys Pro 
    290                 295                 300                 


Asp Asn Pro Trp Glu 
305                 


<210>  3
<211>  1634
<212>  DNA
<213>  Homo sapiens

<400>  3
agtctctcgt catggaatac gcctctgacg cttcactgga ccccgaagcc ccgtggcctc       60

ccgcgccccg cgctcgcgcc tgccgcgtac tgccttgggc cctggtcgcg gggctgctgc      120

tgctgctgct gctcgctgcc gcctgcgccg tcttcctcgc ctgcccctgg gccgtgtccg      180

gggctcgcgc ctcgcccggc tccgcggcca gcccgagact ccgcgagggt cccgagcttt      240

cgcccgacga tcccgccggc ctcttggacc tgcggcaggg catgtttgcg cagctggtgg      300

cccaaaatgt tctgctgatc gatgggcccc tgagctggta cagtgaccca ggcctggcag      360

gcgtgtccct gacggggggc ctgagctaca aagaggacac gaaggagctg gtggtggcca      420

aggctggagt ctactatgtc ttctttcaac tagagctgcg gcgcgtggtg gccggcgagg      480

gctcaggctc cgtttcactt gcgctgcacc tgcagccact gcgctctgct gctggggccg      540

ccgccctggc tttgaccgtg gacctgccac ccgcctcctc cgaggctcgg aactcggcct      600

tcggtttcca gggccgcttg ctgcacctga gtgccggcca gcgcctgggc gtccatcttc      660

acactgaggc cagggcacgc catgcctggc agcttaccca gggcgccaca gtcttgggac      720

tcttccgggt gacccccgaa atcccagccg gactcccttc accgaggtcg gaataacgtc      780

cagcctgggt gcagcccacc tggacagagt ccgaatccta ctccatcctt catggagacc      840

cctggtgctg ggtccctgct gctttctcta cctcaagggg cttggcaggg gtccctgctg      900

ctgacctccc cttgaggacc ctcctcaccc actccttccc caagttggac cttgatattt      960

attctgagcc tgagctcaga taatatatta tatatattat atatatatat atatttctat     1020

ttaaagagga tcctgagttt gtgaatggac ttttttagag gagttgtttt gggggggggg     1080

gggtcttcga cattgccgag gctggtcttg aactcctgga cttagacgat cctcctgcct     1140

cagcctccca agcaactggg attcatcctt tctattaatt cattgtactt atttgcttat     1200

ttgtgtgtat tgagcatctg taatgtgcca gcattgtgcc caggctaggg ggctatagaa     1260

acatctagaa atagactgaa agaaaatctg agttatggta atacgtgagg aatttaaaga     1320

ctcatcccca gcctccacct cctgtgtgat acttgggggc tagctttttt ctttctttct     1380

tttttttgag atggtcttgt tctgtcaacc aggctagaat gcagcggtgc aatcatgagt     1440

caatgcagcc tccagcctcg acctcccgag gctcaggtga tcctcccatc tcagcctctc     1500

gagtagctgg gaccacagtt gtgtgccacc acacttggct aactttttaa tttttttgcg     1560

gagacggtat tgctatgttg ccaaggttgt ttacatgcca gtacaattta taataaacac     1620

tcatttttcc tccc                                                       1634


<210>  4
<211>  254
<212>  PRT
<213>  Homo sapiens

<400>  4

Met Glu Tyr Ala Ser Asp Ala Ser Leu Asp Pro Glu Ala Pro Trp Pro 
1               5                   10                  15      


Pro Ala Pro Arg Ala Arg Ala Cys Arg Val Leu Pro Trp Ala Leu Val 
            20                  25                  30          


Ala Gly Leu Leu Leu Leu Leu Leu Leu Ala Ala Ala Cys Ala Val Phe 
        35                  40                  45              


Leu Ala Cys Pro Trp Ala Val Ser Gly Ala Arg Ala Ser Pro Gly Ser 
    50                  55                  60                  


Ala Ala Ser Pro Arg Leu Arg Glu Gly Pro Glu Leu Ser Pro Asp Asp 
65                  70                  75                  80  


Pro Ala Gly Leu Leu Asp Leu Arg Gln Gly Met Phe Ala Gln Leu Val 
                85                  90                  95      


Ala Gln Asn Val Leu Leu Ile Asp Gly Pro Leu Ser Trp Tyr Ser Asp 
            100                 105                 110         


Pro Gly Leu Ala Gly Val Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu 
        115                 120                 125             


Asp Thr Lys Glu Leu Val Val Ala Lys Ala Gly Val Tyr Tyr Val Phe 
    130                 135                 140                 


Phe Gln Leu Glu Leu Arg Arg Val Val Ala Gly Glu Gly Ser Gly Ser 
145                 150                 155                 160 


Val Ser Leu Ala Leu His Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala 
                165                 170                 175     


Ala Ala Leu Ala Leu Thr Val Asp Leu Pro Pro Ala Ser Ser Glu Ala 
            180                 185                 190         


Arg Asn Ser Ala Phe Gly Phe Gln Gly Arg Leu Leu His Leu Ser Ala 
        195                 200                 205             


Gly Gln Arg Leu Gly Val His Leu His Thr Glu Ala Arg Ala Arg His 
    210                 215                 220                 


Ala Trp Gln Leu Thr Gln Gly Ala Thr Val Leu Gly Leu Phe Arg Val 
225                 230                 235                 240 


Thr Pro Glu Ile Pro Ala Gly Leu Pro Ser Pro Arg Ser Glu 
                245                 250                 


<210>  5
<211>  10351
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  5' homologous arm

<400>  5
tttttggtcc aacagggtag atcagatatg cggtacacac tctcacacca aaagatacac       60

acctgtgtat gctaagtgtg atgggctgga agctatgcag agtccctttc tccagctgac      120

cttcgatgac acaaacacac gttggttgca ttccacatga atgggtaggc acacagtcca      180

agtgcacacc ctggggcagg cagcctcccc gtccccatca tcccacagag agtgggactc      240

aaggctgggc catatgcagg tatggtggtc ttctgaattg ggggcggggg ctaaggaaat      300

ggctcagtgg ctaagagcac ttgctgctct tgtagcggct tagagttcag tccccagcac      360

tcaatccctg ctcataatta ctctagttcc agggaatctg accccctcct ctggcctctc      420

tgaacacttg tagcatccgc tcatagacaa cgcattacac attaataaaa gcaaactaaa      480

ttttaaagag aataagggtg ggcgtgtcca gcagctggaa tgagaatttg taaggcacag      540

aaggaggtgg aggcatttta gactgccttg ccgttaacca ggtcccaggt ggacgaagga      600

gtaaagtagt ctctgaggaa ggtccgatgg gaaacaagct ttctttccta ggctgttaga      660

gtccggtgga atagggagaa cagcggggga tgtgggaagg accagggcgg gctctgggag      720

gctgatagag aagtctgtta agcctacccg gtagggcctg agcagggggg gggggggggg      780

cggagggggg tctttggaga ttggcaggga agcaggcgag gcaagagaac tgaaccgcct      840

gggaagctaa gggagcggga agtaggctgg aagaatgacg tcaaaagtgg gaatccacaa      900

cctcgaggaa gctgttgact ggggaaagtg ggcagggcgt agagagaatg acagagcagc      960

tgggaggggc taagaaagtg ggaggaacct atagagattg agaagtgaga gggacctggg     1020

aagtacacag ctgaaaagta aggatgtggg gctagagaaa gtgaaggagc cattgggagg     1080

gactgcaaat gaaggtttag agagtaacaa ctgggaagtg gacggagcct aaggagaagt     1140

gtatgggctt ggaaaccaga gtctactctc aagtggcacc atgggctctg gccactttcg     1200

tgttgctgat gctggccctg taggaaccat agtgacctgc ctcctcctac aacatcctca     1260

ctgatcgtat ctcgcggtca tacaggcttc tctgggttcc ggtcctcggg ctggtggtcc     1320

tcccggcttc caggttctga tgtcaagttc ttccaaggct cggcaagttt ggggggcaga     1380

cccttccacc tgcatctcat acagcctagg gcgaggatgc cgtccacaag ggggcgcgtg     1440

tgtcccgcgc tgggatccaa ggctgagtag gagggagttc tgttcacaga tctggtacct     1500

ggatgtttta ttggagtatt ggttttgttc ttgttgtttg tttgcttttt tttttaattt     1560

attttatttt gtctttatag gtgtttcgcc tgcctgtatg tctgtgtgaa agtgtcataa     1620

gccttggaac tggagttaca gacaggtctg agctgccata tagctgctgg gaattgaact     1680

tgagtcctct gcaagagcag ccagtgttct taaccatgga gccacctaat cctcactgtt     1740

atttattttt ttttttttta agatagaatc tctcactggt ctgaggagtc cagctatttg     1800

tctagaatag tttgccaatg agttccagga atcctccttt gtctaccttc ccagactaag     1860

attataagca cttgacagct tgtctttttt tttttttttt tttttttcca gacagggttt     1920

ctctgtatag ccctggctgt cctggagctc actttgtaga ccagactggc ctcgaactca     1980

gaaatcggcc tgcctctgcc tcccaagtgc tgggattaaa ggcgtgtggc gccaccacgc     2040

ccggctctta ttattattat taaacaaaac aacaagccag gggtgctggg aaatcaaatc     2100

aggtccccat gcttatgaaa caagtgtcac tggctgagct atgtatgcct ggcatattaa     2160

aaaaaagttt taaagtttta cttgtattta tgtgtatatg tgtgtctcag ggtaagtgca     2220

ggtgagtgta gtgcctattg ctgccagaag aggtgtcaca tccccttgga tctggaatta     2280

caggaggttg tgagccacca tgtgagggtt ggggacttaa ctctggttat ctgaaagagc     2340

agagtaggag tactcttacc tcaacccttt ccatacctct tttatttccc tttctcctct     2400

ctttctgtcc tcacgagaca gggtctatct ctgtagccaa ggctagcctg aaactataca     2460

taggctggcc tcagacttgt gtaatgtcct accttagcat cccaaatgct caggtgacag     2520

atatgaacca ccacaccttg gctgttcagt gtgtttgaca atgatctctc tctctctctc     2580

tctctctctc tctctctctc tctctctctc tctctctctc tctctctctc cccctgccca     2640

gggggctatg gtgtatttgt ggttgctgtg tctgttctat gtcctggctg tgggtgtctt     2700

tgtgtttctg tctaattgtg gctgtctaat ggctacttcc cctggcagca ctggggaatc     2760

ccttacagat gatagtcagg ctgggattcc ctttctactc agcttggttg atttcccatc     2820

actgagttag ctcttatcaa cctctgaggg gtccccagcc tgctcagcca ctcccccatc     2880

tttctcaggg aagaacttat tgttgatgtt aaatttttcc ttcttccaga aagctatggt     2940

caccttttct ttctttctgg gtgcttagtt gactacaggt tgttcatggc taaaaggaag     3000

gaggaggaag atagaaggag aaaaggagga agaggaagag gaggaggagg cagaggaaga     3060

agaggaaccc aaacaaaact ttgtacacat ggaaatgcag gctagagcca taccacagac     3120

tccagtgtgg acaaacctcc ggaagcaatt gtaatgctga ctctttgctc aaactggaag     3180

atcctgtccc cgtggttcaa aggcatgagc tgtctttgct gttgtgtgac tggtgatgtc     3240

atcaatggta atctgaacga ttcccttttg aagactggag agatcatttc cgttctctgc     3300

actttttgct gttatgggct ttgctgttgg tcaaagggtc tcacatagac caggttggcc     3360

tccaactaga cttttaaccg aggctgatct tgaactcctt cctgatcctc ctaactctgc     3420

ctccagagtt ctggctctgt gtagatcctt tcaaacatcc tcacgggtca acccagaggc     3480

aggatttgtg tactggattt cagtgtttca aagtccacat gtagtcactg acacatgcta     3540

ggctgtgtag gctgccagtg gcaaggatgg ctgaacttac tgagtgactg ctgtatgtca     3600

caacatcctg gctccctcac tgtggacacc ttgaattttg aggtagtatt tttttttttt     3660

tttcgagaca aggtttctct gtatagccct ggctgtcctg gaactcactt tgtagatcag     3720

gctggcctcg aactcagaaa tccgcctgcc tctgcctccc aagtgctggg attaagtatt     3780

tttttttaaa gatttatttt atttatatga gtatactgta actgccttca gacacaccag     3840

aagagggcat cagatcccat taccccatta cagatggttg tgagccacca tgtggttgct     3900

ggaaattgaa ctcaggacat ctggaagagc agtcagtgct cttaaccgct gaaccatctc     3960

tccagcctaa gatagtattg ttttaatttc atttcacaga tggggaaatt gaggcaccaa     4020

gaggtaaagg aattccctca ggaggtgggg ctgggatttg aacctatgct gtgtagtttc     4080

catgtgccca ccaggggaga gtcagggaag ttgactttta agcctggctt ctggtatgtg     4140

tatgtaagct cagtacattg gagtctgagg ctgccctggg ctgatagcaa tatcctcact     4200

caagacagga aagcagttga cactcctggc tatgctggtg gccagtacct gtcatcctag     4260

acatttggaa cactgaggca ggaggtgggc atgaacctag gacttggagg tcagcctggg     4320

aaacttacat agactctaca tcaaaaaata aggcaaaaca aaaataaaaa gttaatacta     4380

aattgcttat ggtagtacat atataacatc ccagtttggg ggcttagcat agagcctctg     4440

cctagaatct cccagtgaag ggctgggggc gtggccatag ggtggagccc cgcctattga     4500

ccgccaatga ggggccaggg gcgtgattca gggaatggag cttttgccta ccgcgtatga     4560

gctcattatg gctgacggga gagtgacagt gaaatagaac ggaaccctgc catagaaacc     4620

ttgggataga aacctttact tttcgtctta gaaaatacca agtcatgcct gcctgttctg     4680

gggacctgag aggtgggaga ggagcatcta agccaacact gtagggcggg tccctctaac     4740

tacttgcctc ccttgagttt ttccatgctg tgaggacagc tagggttaac agtcatttca     4800

ggaagacaac tgagtacacc acaggggggg ctattggact ggggttggag gagggagctc     4860

agctctgcat ggtggataga gcttcctgcc cctgcaagtc cctcagcatt gtcagctagg     4920

ctgtagccca gaaagggtgt tccagagctc tgtgaaggca cacagctcag aacatctctg     4980

ggacaccttg gtcagcttgc ttcatagttt acagtgaatc tctggatcta catgcatgtg     5040

ggttgatgtc cccctaggta gaaaccagag agttattttc acttaagttc ctcgcagccc     5100

aagcatgcca ttccagcact tgggaggtgg aggcaggagg aacaagaagt agttggaggc     5160

cattctttgt taagaagtga gctgcctaga ctgggttacg cgaaacccag tctgaagaaa     5220

tatttaggaa gaggaagggg actgatgaga gcgaaagcgg ggcaagagag gatcatgggt     5280

gtgtaggtgg acaggcagcc tgtggtggag ggtgctgagg acctaggttc agttcctggc     5340

actcacatgg catctcacag ttgcctgtaa ctctacttct ggcctctcag aaggcatgta     5400

catggactac agatagacag acagacagac agacagacag acacacacac acacacacac     5460

acacacacac acacacagac ggacctgaga gatggttcag tggctgagag catttgttgc     5520

tatcacagag gacctgggtt ctgttccttg cacgcacatg gtggctcaca actatcctta     5580

attgcaattc caggagatct gacctgggta ctggacctgc acgttggtgc atgcacatac     5640

atgcaggcaa aacagtcata cgcttaaaat atataaatac aaaaacataa ggcacagaaa     5700

caaaccattc ggggtgaata tgatcaaaat gaattatata cataaatgaa aatgtccagg     5760

ctggagagat ggttcagcag ttaagagcac tgactgctct tctaaaggtc ctgagctcaa     5820

atcccagcaa ccacatggtg gctcacagcc attcggaatg agatctgatg ccctcttctg     5880

gtgtgtctga aaacagctat agtgtactta catataataa ataaataaat ctttaaaaga     5940

aaagaaaaga aaatgtccta aagggactca ttgttacata tagctaatat atagctagta     6000

tatattcata aaatatgaaa aacaactcaa acattataga tctcctttgc tacgaatgta     6060

ttctatgtgc aacactgcac acagtggtgc tgggatggaa tccaggtgag tgcttgccat     6120

agagcctgac cctcagaccc tgcgattgaa tgtagtacct gagtgtaatg tattcaagct     6180

taagcatcca gcattgcaag acccatgctg tttaccacag taggcatgga actatacctg     6240

ctttacccac agtcctgcag aatcagcacc aagtttgagc tcttctccat ataccttctt     6300

ctttccctct tatccactct tacacctgcc tgtccatcca ttcacccata caaccatcaa     6360

tccatctatc atccatccac ctgtccatcc atccatccat ccatccatcc atccatccat     6420

ccatccatct actcacttat ccatctgtct gtatgtccat ccatccatct gtctgctcac     6480

ctatctaccc actcactgac tcatatgtca atccatccat ccatccatcc atccatccat     6540

ccatccatcc atccatccat ctgtctgtcc atctgcctgc ctgtccatat agctacctac     6600

tcaccgatcc atctatccat ctgtccatcc atctatccat ctgtctatcc atctacccac     6660

ccacccatct attcatccac ccacctaccc atccatccat ctatccatac attcacccac     6720

acactcaccc atccctgttc cttccttttc ttttttctca cccttcttgc attccgtctt     6780

cccataaata tcatggagac actttttgct ccgtatactg tgggtacctg ggaatacagt     6840

ggatagagac acttttgagg atgccataca tcagtagggg tgggaggcaa tgataagcaa     6900

ggaaagcaat taataaacag tcagtcaagg tgggtgatag ggccagcata acattcttgt     6960

ggcaccagga gtgtctaagt acacttgcta tcctgcacac agttttggga ggctgaggaa     7020

ggaaggtcag ggcaatgtgg caagcctgta attgaaaaca aaaacaaaga gctcatgggg     7080

tggtgtacca cagacctttg agggtggggt tctgtcatct gcgttattgt agatctagat     7140

gctttcctcc cagttcttgt cactgccagc ttaggcaata cttggctgtg ggctgtggtt     7200

ttaattgtaa acagattggc tcaggatctg ggagctagct gctgctgctg ctgctgctgc     7260

tactactact actactacta ctactactac tactactact actactacca ctacggtact     7320

actactacta ctactactac tactactact actactacta ctactaccac tacggtcctg     7380

agatgctaaa tctttcttct tagcaataag gggcaggggg tggactttgt gtgtgagcca     7440

ggggggaggg ggagacttga gttctatccc cagcatctta tacaccagac atggtggcat     7500

ggacctgtca atttagcact ccagaaatgg aggcaggagg attagaagtt tattctttac     7560

tacataggga atgtcaggcc agccttgact acacgagatc ctgttcaaaa acaaattaat     7620

tttaatatta aaatccccct tgtctgtctg tttgtctgtc tgtctgtctc tgtgtgtgtt     7680

tatctgtctg tctcactatt tagccctggc tggtccattc tcattatgta gttcaaggtg     7740

gccttgaatt caccaagacc catctgcttc tacctcctga gtgcaataca taccccctgc     7800

atccagtttt gttttgtttt gtttttttag acagtgtctc ttcatgtagc ccaggctggt     7860

ttttgaactc caaccttcaa acttcagctt cctgaaggct gggctcacag gtgcatacca     7920

tgcatggctt gttctaaatg gtatgaactc tctctctccg tgtgtgtgtg tgttttctgt     7980

ccagaaactc caccaattcc cccccccccc aataataaag caccttcagg ctctgcagga     8040

gagaaagatg gctgagtgga gttactttca gctgagtcag gattccagtt ccctggtgac     8100

atggatgatg agtctgtgag gtggaagtct tcaaactgtg gctttgaaga agttatagct     8160

ggagagagag agagaaagtc ttcatctgcc tttttttttt tctcactgtg atgatggcag     8220

ggatacaaat gaggatgaga caatgtgttc actgtgcagc cgaggcaggg aggggtaaac     8280

tagtccaggc attgaggggt cccttttcgt gagagtcatg taggtgtggg ctgactctga     8340

gcagtgtgtg tccagcagag agaggttgga ccactgtctg cgtgagggcc agagttccca     8400

cagctgagtc accgctggtg ccctgcagct gctccttggg tggaaccttc aatttctaga     8460

tcacccaagt gtcttttgtg tcattttaat gtcccacctc ccccacctct cccctgaccc     8520

caagctgggg ttttcctgta attcccaggg gaagttgatg tggaataaaa cagaaggaag     8580

gggtggctgg tgtctccaga gggggctccg tgcacgtctc ccaggctggg agctcagtag     8640

gttccatgcc cagtatggaa aaaaagcagg tggggcctgg gctgggtctc tgttgtaaga     8700

atcttggccc agtaagctcg aggctttgcg ctccttcccc aacacagaag aagctggatt     8760

tgagggtgta tgcctgtctg tgtctgtatc ccaatatact ggggagggtc agaagttcag     8820

agtcatccta ggctgtctag tgagttggag ggctgcaagg cgaagaccag accctatgta     8880

gaaacaaaca actccccatt ttatagcttg ttgtttcctg ctgagataaa tggtctggtt     8940

atatcagtac tttttttttt tttaattatg tttactgatg gtatgcatgt cgtggtcaaa     9000

gggcactttc aggacaaatt tctgggtgtc agttctttct tcccaccatg taggtcctga     9060

ggactgaact caggccacca ggcttgtgat tatactatta ctggctgagc catctcagca     9120

gatctaacca gatcagaaca ttgaggagtc tgtctccaag gtttgcccag agccagtcat     9180

ctctcagttc ctcttttggg gggtcttctc tgcgcccccc ccttttgcct ctacctcagg     9240

caagaacagt gaaagaatgg gaaattggaa atgtgtccgc tgcctggggg aatttctcta     9300

tctggactct ccagccttct gtttctggag tcctaagaga ctactaacag gaagccccaa     9360

gaaagtgggt ggggacacac caggaaaggc ccagggtaga gatggggtcc tggggaggaa     9420

gaggctgagt gagtgggtgc ctagcaggtc tctttgattc cgctggggat gggtgggcag     9480

ttttggatgt ccctagagtc ctcgacaaaa caacaacaac aaaaaacaaa acaaaacaaa     9540

acaaaacaac aacaaaaccc cctgcattta gggcgtccca gggatgggga gctaggggtt     9600

ggaagaaaaa gggagcagga gagatcagga gagagacaga agtttgagag acagaaaaac     9660

aggaatgaaa atcagcagcg gagaaataac ctaccagtgg ggaacacaga aaaagaaggg     9720

agacagagct gtggattcag gagaggccag ggagggaatg gattccgata tcacatggtt     9780

cccatcatat aaaaagctct ttaatgtgtc agtgttaaac caaatcaaac acacacacac     9840

acacacacac acacacacac acacacacac acacaaaaag ggaagaagga cgggcgggca     9900

cagggcctgg acagggaagg ggaaaggggc gagaaggggg aggggaaggg gggaggagga     9960

gagaaagttc cgggagtcga ggggcggagc gcggagcccg ggaaccccgc ggctgccctc    10020

cctcccttcc ctccccggaa aaggcgcctc ggtagcctat aaagcacggg cactggcggg    10080

agacgtgcac tgaccgaccg tggtaatgga ccagcacaca cttgatgtgg aggataccgc    10140

ggatgccaga catccagcag gtacttcgtg cccctcggat gcggcgctcc tcagagatac    10200

cgggctcctc gcggacgctg cgctcctctc agatactgtg cgccccacaa atgccgcgct    10260

ccccacggat gctgcctacc ctgcggttaa tgttcgggat cgcgaggccg cgtggccgcc    10320

tgcactgaac ttctgttccc gccacccaaa g                                   10351


<210>  6
<211>  4820
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  3' homologous arm

<400>  6
ggctgaagtg gctctgtacc actatccctt ttttgagaca agaaagtatg tagcccaggc       60

tgacctagaa gtccatatat agcctagatt ggccttaaac tcaggccagc atcctgatac      120

ctgagtgctc agttgacagg gtggcagatg tgctgagata gagccagagt ctctcatgca      180

tgtgaggccc atatgcttta tcacagaggg ctctgttcct tggaatccag ctacgaataa      240

gcgaaaaacc aaaaccaaaa caacccccta cctcaaccat ccagtgtgaa agtctgtgat      300

ttctgatgtg acggtactgg actctgtgtg ctatttcgag agacagaacc tgttggagca      360

atacaattat agatacagat aaatgaagga ggagttgtta aggaaattcc cccaacggtg      420

gtcatgtgga ctgagaagtc cctcagctga agactgcagg tgaaggctgg aggaactgga      480

gttcaaggcg ggacagacca ggagcacaag accctgtctc aaaacaaaca gcaaaataaa      540

tcaaactaaa aagaaacaga gacgtcccac aaatcagcta gatctctgta aattcacagg      600

attggaaggt agaggctatc cttgggagtt caaaggctgc ctgggctact tacacaacaa      660

aacaaccacc agcaaacgga ggctgggcta ctcctctgtg agcctgagca tgggtctcac      720

aaggaaggcc tcccaaccat ccaagctgat gtgccagggg ccggcagtgt atttgtaaac      780

tcaactgata agttaagcat ttcctcactc cgtgtgagtc acccagactt gaaacccaca      840

gccactctgg gcctcaacag atttttgaaa aatttccatt tcagtatttc ctagctctga      900

cttcaggtga tttacctcgc tgcctatgag agggtagtgg aaatcccttt gtccctccca      960

cccaatctgg attccgtgtt tagtcacatc acagcctgag gtcaggccca aaggaaacag     1020

tagtgttgaa gttggtttta ctgtattctt caggggtgac agtggaacag cttgagaaac     1080

ctgtcattca gcaaagaagt ggctcactga ggtgagagag gctgggctgg gactgacaaa     1140

ggaggccctg acttccattc cagcacttca taaattactg cataaatgaa catatatgtc     1200

tagatttgca taagaaaaga attcaggact ttgcctcccc cctccagacc ccccctcttt     1260

ttttgtgtgt gtgtgtgtgt tccatgcatc aagtcttcct taatccccct ctattttatc     1320

atttggggca gtgttggtct tctgtccaga ctccaccccc acaattacct ggcaacagcc     1380

aggttaggtt ggcccactat aataggaact gcttggcccc tcttccctct cttactctct     1440

tgtctccctt actcttgctt cccgcttgcc ccctctctcc ccattccctt ctcccctctc     1500

tccacgtggc catagccagc ctctacttct ctactctcta cttctctctg cctttctctg     1560

cctcttaact ctcctcccca tgccctgaat aaactctatt ctatactata ccctcatgtg     1620

gctggttcct caggggaaaa ggatgccttg gcatgggctg ccggggcatc tccttccctc     1680

atacccctgc cagaacatat cttaatagct ctttctcttt ttatgatcac aacaggcagg     1740

gtctttctta ttcctattat tgaacataga ttcttttctc atacaatata tcctgattac     1800

aattttttct ccctctgctt ctcccagttc ttcccctccc tcccctccag atccagtccc     1860

tttctgtctc tcagtaggaa agaacaggct tctaagagat aacaactgga cacgacaaaa     1920

tcaaatataa taagacaaag caaaaccttt catactgcag ttggtcaggt ctgagttcaa     1980

accctgcttc agctagtacc agctaagctg tgtgtacttg ggcaagtgtc tgacttctct     2040

gaacctactg ttcacaataa tgagcataga agctgagttt accgcaaggc tcttggggat     2100

gttaactgag ataataggct ttatgacaca gtgtctgaca ctaaattaaa gcatgaaggt     2160

tgtggtgata agatagacag agagagagag agagagagag agagagagag agagagagag     2220

atatggtttc agaggttcta tcaccatgtc ctgaggcagg caggagatgg gctgaaagat     2280

caggtagcaa tcaagagggc agtgtttcag accactgtaa atctggattc tttggtttct     2340

ggccctggga caagggactg aagtgcatat tttgcatacc aaagcctacc tggcctccag     2400

attatcccag catccctaag tccctacagt ggtatgccct gcctccaatt ctgaactttc     2460

cagcccagag gctgggctct cctttcccag aggctcttcc ctataaaatc cagacactct     2520

ccttccaacc ccccaccaca cacacccttt tctctttctc ttcccctctc ccatctctcc     2580

ccactgtgtc ttcccaagtc tagtccttgg gccagtgaac tcaccagaga gcagtttacc     2640

agtatacctg cccataatat tttctaatct ggcttgaact ggctcatttt gctagcagag     2700

aaataactct ccaaagcctt tcatcaaaac tctagagagg cccggggaag tggctcggtt     2760

aggaaagtgt ttctcgaaag cttgagggcc tgactttgaa tccccagaac ccattttcaa     2820

atgctgaatg tgtagctgaa tgtgtgtcag ggtgcaggcc tttgttccta gcactctgga     2880

ggcaaaggca ggaggatctc tgagtgtgag gccagcttgt ttacagagca tgttccagga     2940

cagccagaac ctcccccatc tctcttcctt ccttccttcc ttccttcctt ccttccttcc     3000

ttccttcctt ccttccttcc tccctccctt cctccctcct tccttccccc tctctcccct     3060

ctctttcccc cctctctctc actcacacac acacacacac acacacacac acacacacac     3120

acacacacac cagcccaaaa aaaaaaaaaa aagctgagtg tggctctgga gagagggtta     3180

atggttccga gagcctgcag ctgttacaga gaaccccagg ttacttccta gcacccattc     3240

caagtggctc accaacactt gtaactccat ctgatgctct cttttgcctc tactggcatt     3300

gtacacatgt gtacacattc cccatttccc atacacacag tacaaagact tcttaaagaa     3360

cattgggcct gaagatgcac aggtgtaact ggcctgtctg tatgagtaat tacaaagaca     3420

caggggagct tcctgtttgg tatcagacta tcgaaaatag ggtatccccg aagttagaat     3480

ctccccagga atctccagct gctggaggtc ccagggctga agcttgtctc ctggagaaag     3540

attgacactt ggttgggcct tgcatggggg gagggagccg agagagtgat gggcgggacc     3600

gtatggtggc aggctatgtg cttatcattt cttactcttt ttgagattta ttttatttta     3660

tgtggatgag tgttatctgt gtgtatctat gcatgctaag tttgtgcctg gtgcccacag     3720

aggccagaag aggatgccag cgtgactgtg agctgctgtg tgggtgcggg tgcaagaaca     3780

gtgggtactc taaccgctgg tatcttcagc ccttgtttct cctgccctct acttaaacct     3840

tggtgccatg ttaggccctc tcaagatgag cttggagggg ggtggctgtc atggatgtct     3900

ttgtctcttt tgccagtgtg gccacataca tttttttctg cttttcacta ttaatttatc     3960

tatttattcg agatagggtc tcaccatgca gccccagatg cctggaccgg gctggcttgg     4020

aactcagaga tatctgcttg ccctttcctc cctagtgcta agattaaaag cgggtgccac     4080

cacatttagt taatttggct gttttagtag gcttattgaa ttaggcttat taaattgaat     4140

ggctgaacct gtgttactgg ggcacagatt gtgatctcta aggccagtag taaatttaca     4200

ctcaaagcac tgggaggtag acacatgaag gtccctgagg aggggtggga tttagaaatg     4260

cacctgaggt tgacctgtgg cctctgcatg cacctgcaca tacctgtgca cacccacaac     4320

acctgctcag agtgatgcgt tgccaagcag aacagacaca tctagttagc ttattggagg     4380

actgcttagt ttgcaagatg agcttgaaag gggttggggg ggagcaggat ggaggcagag     4440

atttatggaa gaggctgtgg aatgttctag aagaggggta gttgaatgaa cagtacagct     4500

gagagtcgat attatttatt tatttattta tttatttatt tatttattca tctatctatc     4560

tatctatcta tctatctatc tatggagaca tctatctatc tatctatcta tctatctatc     4620

tatctatcta tctatctatc tatctatcta tctatctatt tgacaaaggg tctctctata     4680

gctctggctg tcctgtagtt tgggctatag accaggctgg ccttggactc agagatctgc     4740

ctgcctctga ctcccaagtc ctgggaataa aggcgtgtgc cattactacc acctcagtgt     4800

ggtggtgaca tttgtcccat                                                 4820


<210>  7
<211>  3955
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  a 3955 bp genomic DNA sequence starting from within exon 1 and ending within exon 3 of the human TNFSF9 gene

<400>  7
gtactgcctt gggccctggt cgcggggctg ctgctgctgc tgctgctcgc tgccgcctgc       60

gccgtcttcc tcgcctgccc ctgggccgtg tccggggctc gcgcctcgcc cggctccgcg      120

gccagcccga gactccgcga gggtcccgag ctttcgcccg acgatcccgc cggcctcttg      180

gacctgcggc aggtgagacg tgccccgacc ctcggtagct ggtctcgcgg gagaccccta      240

ccgcccctct gggactccct tctccctccc gcacccccag ggacacctgt tctacactcc      300

cggccgggga gaggagaccc accggggctc ccattctcca tctagcaccg aggccggggg      360

ggcacacctt tcatcccgca cccctacgac acctcatctg taccccaggc cgggggcggg      420

gaggagaccg cccaacagtt ctttttggac cccccaaggg tctccttctt ctagtccggg      480

gggcacccct ttcatcctgc gcccgctacg agaccctatc tgtatcccgg gagggggaga      540

ggagaccccc acaagttctt tttggacctc caagggctct ccttctccgt cttgcacggg      600

agggcacccc tttcattccg catcccgaga ccccatcagc accccaggcc aggaggagga      660

gacccccaca gtcctcaacc cctcagggat acgtcttctg caccccgggt cggagaaagg      720

ctggcttccc tccatgtggc agtgggtggg ggcacccctc ttcattccgc attcccaagg      780

caccccatct gcaccctgga cgggggaccc tccgcggttc tccaaccctc gacggcttcc      840

tttctctatg taggacttag gacattgagg gcacctcttt ttaccccgca cccccacaag      900

ctctgcatct ctggggggaa ccttttttcc atccccgatc cgaggggggc acttcctctt      960

tatctgggac cgccaaggag acccccagtt cctttgctaa ctcccaaaga gccttatccc     1020

caacatctga ggtacccctc tccctttcaa gacccccagg ggaatacccc caagggggct     1080

ggaaagaaga gggatcgctt ttccctcctg aattcttgga gatctgtcct tggggcaggt     1140

tgagccacca gcttcgtgtg tgtgtgtgtg tgtgtgtgtg tgtgtgttcg tgtttgtgtg     1200

ggtgtttgtg ttcgtgtgtg tgtgttcgtg tgggggtgcg tatgtgtgtg tgttcgtggg     1260

tgtgtttgtg ttcgtgtggg tgtgtgttcg tgtgggtgtt tgtgtttgtt cgttcgtgtg     1320

ggtgtttgtg ttcatgtggg tgtgtttgga tatttgtgtt cgtgtgtgtc tgtgtgtgtt     1380

cgtgtgggtg tttgtgtgtg tttgtgtttg cgttcgtgtg tgtgttcgtg tttgttcgtg     1440

tgtctgtgtg ttaatgtggg tgttcgtgtg tgtgttcgtt tgtgtttgtg ttcgtgtgtt     1500

tgtgtgtttg tgtgtgtgtg tgtgcggtct ctgttcttta gttgggaggg aagggaagcg     1560

taggcttcag gtcggcacag actctgggga ccctgacagc tgaagtgagt ggggacagaa     1620

cctccatttt ctaggggaac ccccatccac tttcctcctt tctactttta acagggcatg     1680

tttgcgcagc tggtggccca aaatggtaag tatcctccgc cacttccggt ccctggcccc     1740

ccaccatccc caccccggga tacgaagaag ggggaacctg gagagtgagg ctctgccgca     1800

cactggcttt gacccttgac cgctgctgtc tctgaaagct gctacttccc ctctttgaac     1860

gccaccgatc cctctttctg acttgctctg actctctgga tgccatggcc tccccatcag     1920

acccccatct gggcccacct gggacccctg ccctctcaga gctggggctt gacaccccca     1980

acccccagcc tggttttgtg tctctggcct ccttcttttc gaaaccctct tccccgctgc     2040

ttttcttccc tctttcctgc cccttcccca ctctcccagc ctctcttccc tacctcttcc     2100

cctcgcccag agcctcctcc ttactcccat tctcttcccc atccccaggc cctcctcctg     2160

tccccttccc tccccctaga ccctcctccc tgccccttcc ccaaaccctc cccagcccca     2220

tgctctccca gtttccaaga cactcctccc agcaccttcc ctccccgtcc agagacttct     2280

tccccgctcg agacctcttc ccccttcccc tcccagagac ccccttcccc cttcccctct     2340

ccatctagag atcacttccc cctttcccct ccccctccag aaaccccttc ccccttccct     2400

ctcccctcca gagacccctt ccccctccaa agaccccttc ccccttcctt ccccctccag     2460

agaccccttt ccccttccct ccccttccag agaccccttc cccctccccc tccaaagacc     2520

ccttcctcct tcccctccct ctccagagac cccttccccc ttccctctcc ctccagagac     2580

cccttccccc ttccctgccc cctccagagt ccccttcccc tccagaggcc ccttccccct     2640

tccccctccc cctccagaga caccttctcc cttctccccc tccagagacc ccttccccct     2700

tccctccccc tgcctaagac tcccctccct gccatcttct ctccttggtg cttccttctc     2760

cctaacccct cccccacccc ttcctgctcc ctttgccttt cttcgaagtc ctctcttacc     2820

aggtcccctg tccacccctc ttaaagttcc cttgattccc tgatggatcc ttcctctaga     2880

acttcctcct ttcctaacag tcttccctct ccctcctagc tccctgtcca cctctcctct     2940

cccctttcct tccttctctc ccttctcctc cccccatctc catcctgtcc gagatctgct     3000

gctccctcca accccctcac cgccctctcc aggagtcccc ttacccctcc ccgaggcctc     3060

ttccagccag actcgcctgg ccttttgctt ttcaccccct cttcctcttc ctgcatgtct     3120

ttccccgcac ccgcatcact ccttccccac ccaacctctt ggagttttgc cctgtcccga     3180

ctcttgtcct tctccctgga ttcccttcct ctgttctatc cccgtctttc cctcccctag     3240

ctctacccct gctcagagtc ccgcccccaa caacctcagt tctcttcaat cagcaccccc     3300

ccaacgcccc ccccacccag gctccccgct ctgctcccct gtcccgctcc ctgccccgcc     3360

attccccgcc ccccggcccc tgacccgttc ttttctccca gggctgcgct gacatgttcg     3420

gtgctcagcc acgctcagct gtgctgggac atgctcagct aagctaagtg catgctttcc     3480

tcccacagtt ctgctgatcg atgggcccct gagctggtac agtgacccag gcctggcagg     3540

cgtgtccctg acggggggcc tgagctacaa agaggacacg aaggagctgg tggtggccaa     3600

ggctggagtc tactatgtct tctttcaact agagctgcgg cgcgtggtgg ccggcgaggg     3660

ctcaggctcc gtttcacttg cgctgcacct gcagccactg cgctctgctg ctggggccgc     3720

cgccctggct ttgaccgtgg acctgccacc cgcctcctcc gaggctcgga actcggcctt     3780

cggtttccag ggccgcttgc tgcacctgag tgccggccag cgcctgggcg tccatcttca     3840

cactgaggcc agggcacgcc atgcctggca gcttacccag ggcgccacag tcttgggact     3900

cttccgggtg acccccgaaa tcccagccgg actcccttca ccgaggtcgg aataa          3955


<210>  8
<211>  80
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  synthesized sequence

<400>  8
cgaaatccca gccggactcc cttcaccgag gtcggaataa gaactatcct tcttgtgact       60

cctagttgct aagtcctcaa                                                   80


<210>  9
<211>  80
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  synthesized sequence

<400>  9
attccccagg ggagtgccta taccagatct taaaataatt gatatcgaat tccgaagttc       60

ctattctcta gaaagtatag                                                   80


<210>  10
<211>  80
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  synthesized sequence

<400>  10
gtataggaac ttcatcagtc aggtacataa tggtggatcc ggctgaagtg gctctgtacc       60

actatccctt ttttgagaca                                                   80


<210>  11
<211>  1236
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  TNFSF9 mRNA sequence of the modified humanized mouse 

<400>  11
ataaagcacg ggcactggcg ggagacgtgc actgaccgac cgtggtaatg gaccagcaca       60

cacttgatgt ggaggatacc gcggatgcca gacatccagc aggtacttcg tgcccctcgg      120

atgcggcgct cctcagagat accgggctcc tcgcggacgc tgcgctcctc tcagatactg      180

tgcgccccac aaatgccgcg ctccccacgg atgctgccta ccctgcggtt aatgttcggg      240

atcgcgaggc cgcgtggccg cctgcactga acttctgttc ccgccaccca aaggtactgc      300

cttgggccct ggtcgcgggg ctgctgctgc tgctgctgct cgctgccgcc tgcgccgtct      360

tcctcgcctg cccctgggcc gtgtccgggg ctcgcgcctc gcccggctcc gcggccagcc      420

cgagactccg cgagggtccc gagctttcgc ccgacgatcc cgccggcctc ttggacctgc      480

ggcagggcat gtttgcgcag ctggtggccc aaaatgttct gctgatcgat gggcccctga      540

gctggtacag tgacccaggc ctggcaggcg tgtccctgac ggggggcctg agctacaaag      600

aggacacgaa ggagctggtg gtggccaagg ctggagtcta ctatgtcttc tttcaactag      660

agctgcggcg cgtggtggcc ggcgagggct caggctccgt ttcacttgcg ctgcacctgc      720

agccactgcg ctctgctgct ggggccgccg ccctggcttt gaccgtggac ctgccacccg      780

cctcctccga ggctcggaac tcggccttcg gtttccaggg ccgcttgctg cacctgagtg      840

ccggccagcg cctgggcgtc catcttcaca ctgaggccag ggcacgccat gcctggcagc      900

ttacccaggg cgccacagtc ttgggactct tccgggtgac ccccgaaatc ccagccggac      960

tcccttcacc gaggtcggaa taagaactat ccttcttgtg actcctagtt gctaagtcct     1020

caagctgcta tgttttatgg ggtctgagca ggggtccctt ccatgacttt ctcttgtctt     1080

taactggact tggtatttat tctgagcata gctcagacaa gactttatat aattcactag     1140

atagcattag taaactgctg ggcagctgct agataaaaaa aaatttctaa atcaaagttt     1200

atatttatat taatatataa aaataaatgt gtttgt                               1236


<210>  12
<211>  311
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  TNFSF9 protein expressed by the modified humanized mouse

<400>  12

Met Asp Gln His Thr Leu Asp Val Glu Asp Thr Ala Asp Ala Arg His 
1               5                   10                  15      


Pro Ala Gly Thr Ser Cys Pro Ser Asp Ala Ala Leu Leu Arg Asp Thr 
            20                  25                  30          


Gly Leu Leu Ala Asp Ala Ala Leu Leu Ser Asp Thr Val Arg Pro Thr 
        35                  40                  45              


Asn Ala Ala Leu Pro Thr Asp Ala Ala Tyr Pro Ala Val Asn Val Arg 
    50                  55                  60                  


Asp Arg Glu Ala Ala Trp Pro Pro Ala Leu Asn Phe Cys Ser Arg His 
65                  70                  75                  80  


Pro Lys Val Leu Pro Trp Ala Leu Val Ala Gly Leu Leu Leu Leu Leu 
                85                  90                  95      


Leu Leu Ala Ala Ala Cys Ala Val Phe Leu Ala Cys Pro Trp Ala Val 
            100                 105                 110         


Ser Gly Ala Arg Ala Ser Pro Gly Ser Ala Ala Ser Pro Arg Leu Arg 
        115                 120                 125             


Glu Gly Pro Glu Leu Ser Pro Asp Asp Pro Ala Gly Leu Leu Asp Leu 
    130                 135                 140                 


Arg Gln Gly Met Phe Ala Gln Leu Val Ala Gln Asn Val Leu Leu Ile 
145                 150                 155                 160 


Asp Gly Pro Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala Gly Val Ser 
                165                 170                 175     


Leu Thr Gly Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu Leu Val Val 
            180                 185                 190         


Ala Lys Ala Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu Leu Arg Arg 
        195                 200                 205             


Val Val Ala Gly Glu Gly Ser Gly Ser Val Ser Leu Ala Leu His Leu 
    210                 215                 220                 


Gln Pro Leu Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala Leu Thr Val 
225                 230                 235                 240 


Asp Leu Pro Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala Phe Gly Phe 
                245                 250                 255     


Gln Gly Arg Leu Leu His Leu Ser Ala Gly Gln Arg Leu Gly Val His 
            260                 265                 270         


Leu His Thr Glu Ala Arg Ala Arg His Ala Trp Gln Leu Thr Gln Gly 
        275                 280                 285             


Ala Thr Val Leu Gly Leu Phe Arg Val Thr Pro Glu Ile Pro Ala Gly 
    290                 295                 300                 


Leu Pro Ser Pro Arg Ser Glu 
305                 310     


<210>  13
<211>  1475
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  3' homologous arm

<400>  13
gaactatcct tcttgtgact cctagttgct aagtcctcaa gctgctatgt tttatggggt       60

ctgagcaggg gtcccttcca tgactttctc ttgtctttaa ctggacttgg tatttattct      120

gagcatagct cagacaagac tttatataat tcactagata gcattagtaa actgctgggc      180

agctgctaga taaaaaaaaa tttctaaatc aaagtttata tttatattaa tatataaaaa      240

taaatgtgtt tgtaaataag ccttttatta ttttccttgt ctggttttaa attttcatgt      300

ctatgggtat ggtgttcatt tatgaatgtg tctttgtata cgtgtgtgtg tgtgtgtgtg      360

tgtgtgtgtg tgtgtgtgtg tgtgtatttg tagagaggat agagtttggc tcagtgtctt      420

cttcagtcat tctccatctt gttttttgag acaagttctc ttactgagct tggaattcac      480

ggtttctgca aggctgtctg gccattgggc cccaagaatt ccccagggga gtgcctatac      540

cagatcttaa aataattggc tgaagtggct ctgtaccact atcccttttt tgagacaaga      600

aagtatgtag cccaggctga cctagaagtc catatatagc ctagattggc cttaaactca      660

ggccagcatc ctgatacctg agtgctcagt tgacagggtg gcagatgtgc tgagatagag      720

ccagagtctc tcatgcatgt gaggcccata tgctttatca cagagggctc tgttccttgg      780

aatccagcta cgaataagcg aaaaaccaaa accaaaacaa ccccctacct caaccatcca      840

gtgtgaaagt ctgtgatttc tgatgtgacg gtactggact ctgtgtgcta tttcgagaga      900

cagaacctgt tggagcaata caattataga tacagataaa tgaaggagga gttgttaagg      960

aaattccccc aacggtggtc atgtggactg agaagtccct cagctgaaga ctgcaggtga     1020

aggctggagg aactggagtt caaggcggga cagaccagga gcacaagacc ctgtctcaaa     1080

acaaacagca aaataaatca aactaaaaag aaacagagac gtcccacaaa tcagctagat     1140

ctctgtaaat tcacaggatt ggaaggtaga ggctatcctt gggagttcaa aggctgcctg     1200

ggctacttac acaacaaaac aaccaccagc aaacggaggc tgggctactc ctctgtgagc     1260

ctgagcatgg gtctcacaag gaaggcctcc caaccatcca agctgatgtg ccaggggccg     1320

gcagtgtatt tgtaaactca actgataagt taagcatttc ctcactccgt gtgagtcacc     1380

cagacttgaa acccacagcc actctgggcc tcaacagatt tttgaaaaat ttccatttca     1440

gtatttccta gctctgactt caggtgattt acctc                                1475


<210>  14
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA1targeting site

<400>  14
gctctatggc ctagtcgctt tgg                                               23


<210>  15
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA2targeting site

<400>  15
ggctcggtgc gggtgaagat agg                                               23


<210>  16
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA3targeting site

<400>  16
tcgggtaccc aggttgggcg agg                                               23


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

<220>
<223>  sgRNA4targeting site

<400>  17
gcgctggccg aggctcggtg cgg                                               23


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

<220>
<223>  sgRNA5targeting site

<400>  18
tcttcacccg caccgagcct cgg                                               23


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

<220>
<223>  sgRNA6targeting site

<400>  19
tgtgagcgct ggccgaggct cgg                                               23


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

<220>
<223>  sgRNA7targeting site

<400>  20
tcccgccacc caaagctcta tgg                                               23


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

<220>
<223>  sgRNA8targeting site

<400>  21
ggtacccagg ttgggcgagg tgg                                               23


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

<220>
<223>  sgRNA9targeting site

<400>  22
acaagttagt ggaccgttcc tgg                                               23


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

<220>
<223>  sgRNA10targeting site

<400>  23
tgtgaaaccc gacaacccat ggg                                               23


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

<220>
<223>  sgRNA11targeting site

<400>  24
ttgtgaaacc cgacaaccca tgg                                               23


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

<220>
<223>  sgRNA12targeting site

<400>  25
gctggccacc gcctcagtgt ggg                                               23


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

<220>
<223>  sgRNA13targeting site

<400>  26
ggctggccac cgcctcagtg tgg                                               23


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

<220>
<223>  sgRNA14targeting site

<400>  27
ctccatggag aacaagttag tgg                                               23


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

<220>
<223>  sgRNA15targeting site

<400>  28
ggtctgaggg cttatctgca tgg                                               23


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

<220>
<223>  sgRNA16targeting site

<400>  29
cccaggatgc atacagagac tgg                                               23


<210>  30
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA1sequence upstream

<400>  30
gctctatggc ctagtcgctt                                                   20


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

<220>
<223>  sgRNA1sequence forward oligonucleotide

<400>  31
taggctctat ggcctagtcg ctt                                               23


<210>  32
<211>  19
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA1sequence downstream

<400>  32
aagcgactag gccatagag                                                    19


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

<220>
<223>  sgRNA1sequence reverse oligonucleotide

<400>  33
aaacaagcga ctaggccata gag                                               23


<210>  34
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA10sequence upstream

<400>  34
tgtgaaaccc gacaacccat                                                   20


<210>  35
<211>  24
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA10sequence forward oligonucleotide

<400>  35
taggtgtgaa acccgacaac ccat                                              24


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

<220>
<223>  sgRNA10sequence downstream

<400>  36
atgggttgtc gggtttcaca                                                   20


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

<220>
<223>  sgRNA10sequence reverse oligonucleotide

<400>  37
aaacatgggt tgtcgggttt caca                                              24


<210>  38
<211>  132
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA scaffold

<400>  38
gaattctaat acgactcact atagggggtc ttcgagaaga cctgttttag agctagaaat       60

agcaagttaa aataaggcta gtccgttatc aacttgaaaa agtggcaccg agtcggtgct      120

tttaaaggat cc                                                          132


<210>  39
<211>  25
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  PCR primer CL-F

<400>  39
agctcagtag gttccatgcc cagta                                             25


<210>  40
<211>  24
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  PCR primer CL-R

<400>  40
gaaggtgctg ggaggagtgt cttg                                              24


<210>  41
<211>  22
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  PCR primer R-GT-F

<400>  41
ccctctcaga gctggggctt ga                                                22


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

<220>
<223>  PCR primer R-GT-R

<400>  42
tctctcacct cagtgagcca cttct                                             25


<210>  43
<211>  22
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  PCR primer P1-F

<400>  43
ccgaccctcg gtagctggtc tc                                                22


<210>  44
<211>  24
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  PCR primers P1-R

<400>  44
ctcccgtgca agacggagaa ggag                                              24


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

<220>
<223>  PCR primer P2-F

<400>  45
tgagctgttg ggagaccttg actta                                             25


<210>  46
<211>  26
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  PCR primer P2-R

<400>  46
ggagttgact cagtggtcag cactta                                            26


<210>  47
<211>  25
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  PCR primer WT-F

<400>  47
acacacttga tgtggaggat accgc                                             25


<210>  48
<211>  26
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  PCR primer Mut-R2

<400>  48
agctgcccag cagtttacta atgcta                                            26


<210>  49
<211>  22
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Mut-R

<400>  49
cgagaccagc taccgagggt cg                                                22


<210>  50
<211>  1494
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  5' homologous arm

<400>  50
aggcgaagac cagaccctat gtagaaacaa acaactcccc attttatagc ttgttgtttc       60

ctgctgagat aaatggtctg gttatatcag tacttttttt ttttttaatt atgtttactg      120

atggtatgca tgtcgtggtc aaagggcact ttcaggacaa atttctgggt gtcagttctt      180

tcttcccacc atgtaggtcc tgaggactga actcaggcca ccaggcttgt gattatacta      240

ttactggctg agccatctca gcagatctaa ccagatcaga acattgagga gtctgtctcc      300

aaggtttgcc cagagccagt catctctcag ttcctctttt ggggggtctt ctctgcgccc      360

cccccttttg cctctacctc aggcaagaac agtgaaagaa tgggaaattg gaaatgtgtc      420

cgctgcctgg gggaatttct ctatctggac tctccagcct tctgtttctg gagtcctaag      480

agactactaa caggaagccc caagaaagtg ggtggggaca caccaggaaa ggcccagggt      540

agagatgggg tcctggggag gaagaggctg agtgagtggg tgcctagcag gtctctttga      600

ttccgctggg gatgggtggg cagttttgga tgtccctaga gtcctcgaca aaacaacaac      660

aacaaaaaac aaaacaaaac aaaacaaaac aacaacaaaa ccccctgcat ttagggcgtc      720

ccagggatgg ggagctaggg gttggaagaa aaagggagca ggagagatca ggagagagac      780

agaagtttga gagacagaaa aacaggaatg aaaatcagca gcggagaaat aacctaccag      840

tggggaacac agaaaaagaa gggagacaga gctgtggatt caggagaggc cagggaggga      900

atggattccg atatcacatg gttcccatca tataaaaagc tctttaatgt gtcagtgtta      960

aaccaaatca aacacacaca cacacacaca cacacacaca cacacacaca cacacacaaa     1020

aagggaagaa ggacgggcgg gcacagggcc tggacaggga aggggaaagg ggcgagaagg     1080

gggaggggaa ggggggagga ggagagaaag ttccgggagt cgaggggcgg agcgcggagc     1140

ccgggaaccc cgcggctgcc ctccctccct tccctccccg gaaaaggcgc ctcggtagcc     1200

tataaagcac gggcactggc gggagacgtg cactgaccga ccgtggtaat ggaccagcac     1260

acacttgatg tggaggatac cgcggatgcc agacatccag caggtacttc gtgcccctcg     1320

gatgcggcgc tcctcagaga taccgggctc ctcgcggacg ctgcgctcct ctcagatact     1380

gtgcgcccca caaatgccgc gctccccacg gatgctgcct accctgcggt taatgttcgg     1440

gatcgcgagg ccgcgtggcc gcctgcactg aacttctgtt cccgccaccc aaag           1494


<210>  51
<211>  2134
<212>  DNA
<213>  Mus musculus

<400>  51
ttcctgaaat tcaggtgctg caggcagccc tcagcacaga gagctgacag ggaccctggg       60

tcaggggttc tgagttccag ctgccactat tcttcttcac ctttggtgtc ctgtgcatgt      120

gacatttcgc catgggaaac aactgttaca acgtggtggt cattgtgctg ctgctagtgg      180

gctgtgagaa ggtgggagcc gtgcagaact cctgtgataa ctgtcagcct ggtactttct      240

gcagaaaata caatccagtc tgcaagagct gccctccaag taccttctcc agcataggtg      300

gacagccgaa ctgtaacatc tgcagagtgt gtgcaggcta tttcaggttc aagaagtttt      360

gctcctctac ccacaacgcg gagtgtgagt gcattgaagg attccattgc ttggggccac      420

agtgcaccag atgtgaaaag gactgcaggc ctggccagga gctaacgaag cagggttgca      480

aaacctgtag cttgggaaca tttaatgacc agaacggtac tggcgtctgt cgaccctgga      540

cgaactgctc tctagacgga aggtctgtgc ttaagaccgg gaccacggag aaggacgtgg      600

tgtgtggacc ccctgtggtg agcttctctc ccagtaccac catttctgtg actccagagg      660

gaggaccagg agggcactcc ttgcaggtcc ttaccttgtt cctggcgctg acatcggctt      720

tgctgctggc cctgatcttc attactctcc tgttctctgt gctcaaatgg atcaggaaaa      780

aattccccca catattcaag caaccattta agaagaccac tggagcagct caagaggaag      840

atgcttgtag ctgccgatgt ccacaggaag aagaaggagg aggaggaggc tatgagctgt      900

gatgtactat cctaggagat gtgtgggccg aaaccgagaa gcactaggac cccaccatcc      960

tgtggaacag cacaagcaac cccaccaccc tgttcttaca catcatccta gatgatgtgt     1020

gggcgcgcac ctcatccaag tctcttctaa cgctaacata tttgtcttta ccttttttaa     1080

atcttttttt aaatttaaat tttatgtgtg tgagtgtttt gcctgcctgt atgcacacgt     1140

gtgtgtgtgt gtgtgtgtga cactcctgat gcctgaggag gtcagaagag aaagggttgg     1200

ttccataaga actggagtta tggatggctg tgagcctttg tgtgggtgct aggaatcaaa     1260

cctgggtcct ctacaagggc agccagtgct cttaaccact gagtcagctt tccagccctg     1320

ccctggacag tttttaaaat ttaacttaat tttttttttt ttttacttaa gcccttaaca     1380

tttttaatag gactgtggga agatcaattt ctagattctc cttaacaata tacatcatat     1440

acatatacac atacatatac atatacatat atattctgag aaaatgacag tttcagttgg     1500

atctcataga ccaatggtcc agttaaaata actgtaaaat cagtgtgtgt gtgtgtgtgt     1560

gtgtgtgtgt gcaaatatga tgcatgacaa tagccataag atgcagtata ttaccctatc     1620

ccattttcct ttggtttctc actcactata ataacacctc cactgtctga agggggagac     1680

ccatgcatcc ctgtctggag gaagcctgac agattttgag gggaatcttc agagcagttc     1740

aagggcctgc ttctcctgtt tcctctgtgt caggcttttc aataaaaagg ccgtttagga     1800

aagggacaaa gcactgtgag gtggggaaca cctgtgaact cacagtagga acgcggcctt     1860

ccagtccacc atgggcagac atggctgccg cttgcctctg catgactcct ggacagctca     1920

agagctgaga atggttgtta cttttcttta ttttgagaca gcacctccct ctgtagtgct     1980

ggctggcctg gaagtcacag aaatcctcct gcctctgctt ccagagtact gggtcttaaa     2040

ctgttcacca cgtctcccct ccccaacccc caaactagcc tttccatttt taaaagccag     2100

ctaaaaatat taaagttgtg ctcttacaaa agtc                                 2134


<210>  52
<211>  256
<212>  PRT
<213>  Mus musculus

<400>  52

Met Gly Asn Asn Cys Tyr Asn Val Val Val Ile Val Leu Leu Leu Val 
1               5                   10                  15      


Gly Cys Glu Lys Val Gly Ala Val Gln Asn Ser Cys Asp Asn Cys Gln 
            20                  25                  30          


Pro Gly Thr Phe Cys Arg Lys Tyr Asn Pro Val Cys Lys Ser Cys Pro 
        35                  40                  45              


Pro Ser Thr Phe Ser Ser Ile Gly Gly Gln Pro Asn Cys Asn Ile Cys 
    50                  55                  60                  


Arg Val Cys Ala Gly Tyr Phe Arg Phe Lys Lys Phe Cys Ser Ser Thr 
65                  70                  75                  80  


His Asn Ala Glu Cys Glu Cys Ile Glu Gly Phe His Cys Leu Gly Pro 
                85                  90                  95      


Gln Cys Thr Arg Cys Glu Lys Asp Cys Arg Pro Gly Gln Glu Leu Thr 
            100                 105                 110         


Lys Gln Gly Cys Lys Thr Cys Ser Leu Gly Thr Phe Asn Asp Gln Asn 
        115                 120                 125             


Gly Thr Gly Val Cys Arg Pro Trp Thr Asn Cys Ser Leu Asp Gly Arg 
    130                 135                 140                 


Ser Val Leu Lys Thr Gly Thr Thr Glu Lys Asp Val Val Cys Gly Pro 
145                 150                 155                 160 


Pro Val Val Ser Phe Ser Pro Ser Thr Thr Ile Ser Val Thr Pro Glu 
                165                 170                 175     


Gly Gly Pro Gly Gly His Ser Leu Gln Val Leu Thr Leu Phe Leu Ala 
            180                 185                 190         


Leu Thr Ser Ala Leu Leu Leu Ala Leu Ile Phe Ile Thr Leu Leu Phe 
        195                 200                 205             


Ser Val Leu Lys Trp Ile Arg Lys Lys Phe Pro His Ile Phe Lys Gln 
    210                 215                 220                 


Pro Phe Lys Lys Thr Thr Gly Ala Ala Gln Glu Glu Asp Ala Cys Ser 
225                 230                 235                 240 


Cys Arg Cys Pro Gln Glu Glu Glu Gly Gly Gly Gly Gly Tyr Glu Leu 
                245                 250                 255     


<210>  53
<211>  6001
<212>  DNA
<213>  Homo sapiens

<400>  53
caaggaggga tcccacagat gtcacagggc tgtcacagag ctgtggtggg aatttcccat       60

gagaccccgc ccctggctga gtcaccgcac tcctgtgttt gacctgaagt cctctcgagc      120

tgcagaagcc tgaagaccaa ggagtggaaa gttctccggc agccctgaga tctcaagagt      180

gacatttgtg agaccagcta atttgattaa aattctcttg gaatcagctt tgctagtatc      240

atacctgtgc cagatttcat catgggaaac agctgttaca acatagtagc cactctgttg      300

ctggtcctca actttgagag gacaagatca ttgcaggatc cttgtagtaa ctgcccagct      360

ggtacattct gtgataataa caggaatcag atttgcagtc cctgtcctcc aaatagtttc      420

tccagcgcag gtggacaaag gacctgtgac atatgcaggc agtgtaaagg tgttttcagg      480

accaggaagg agtgttcctc caccagcaat gcagagtgtg actgcactcc agggtttcac      540

tgcctggggg caggatgcag catgtgtgaa caggattgta aacaaggtca agaactgaca      600

aaaaaaggtt gtaaagactg ttgctttggg acatttaacg atcagaaacg tggcatctgt      660

cgaccctgga caaactgttc tttggatgga aagtctgtgc ttgtgaatgg gacgaaggag      720

agggacgtgg tctgtggacc atctccagcc gacctctctc cgggagcatc ctctgtgacc      780

ccgcctgccc ctgcgagaga gccaggacac tctccgcaga tcatctcctt ctttcttgcg      840

ctgacgtcga ctgcgttgct cttcctgctg ttcttcctca cgctccgttt ctctgttgtt      900

aaacggggca gaaagaaact cctgtatata ttcaaacaac catttatgag accagtacaa      960

actactcaag aggaagatgg ctgtagctgc cgatttccag aagaagaaga aggaggatgt     1020

gaactgtgaa atggaagtca atagggctgt tgggactttc ttgaaaagaa gcaaggaaat     1080

atgagtcatc cgctatcaca gctttcaaaa gcaagaacac catcctacat aatacccagg     1140

attcccccaa cacacgttct tttctaaatg ccaatgagtt ggcctttaaa aatgcaccac     1200

tttttttttt tttttgacag ggtctcactc tgtcacccag gctggagtgc agtggcacca     1260

ccatggctct ctgcagcctt gacctctggg agctcaagtg atcctcctgc ctcagtctcc     1320

tgagtagctg gaactacaag gaagggccac cacacctgac taactttttt gttttttgtt     1380

tggtaaagat ggcatttcac catgttgtac aggctggtct caaactccta ggttcacttt     1440

ggcctcccaa agtgctggga ttacagacat gaactgccag gcccggccaa aataatgcac     1500

cacttttaac agaacagaca gatgaggaca gagctggtga taaaaaaaaa aaaaaaaaag     1560

cattttctag ataccactta acaggtttga gctagttttt ttgaaatcca aagaaaatta     1620

tagtttaaat tcaattacat agtccagtgg tccaactata attataatca aaatcaatgc     1680

aggtttgttt tttggtgcta atatgacata tgacaataag ccacgaggtg cagtaagtac     1740

ccgactaaag tttccgtggg ttctgtcatg taacacgaca tgctccaccg tcagggggga     1800

gtatgagcag agtgcctgag tttagggtca aggacaaaaa acctcaggcc tggaggaagt     1860

tttggaaaga gttcaagtgt ctgtatatcc tatggtcttc tccatcctca caccttctgc     1920

ctttgtcctg ctccctttta agccaggtta cattctaaaa attcttaact tttaacataa     1980

tattttatac caaagccaat aaatgaactg catatgatag gtatgaagta cagtgagaaa     2040

attaacacct gtgagctcat tgtcctacca cagcactaga gtgggggccg ccaaactccc     2100

atggccaaac ctggtgcacc atttgccttt gtttgtctgt tggtttgctt gagacagtct     2160

tgctctgttg cccaggctgg aatggagtgg ctattcacag gcacaatcat agcacacttt     2220

agccttaaac tcctgggctc aagtgatcca cccgcctcag tctcccaagt agctgggatt     2280

acaggtgcaa acctggcatg cctgccattg tttggcttat gatctaagga tagcttttta     2340

aattttattc attttatttt tttttgagac agtgtctcac tctgtctccc aggctggagt     2400

acagtggtac aatcttggat caccgcctcc cagtttcaag tgatctccct gcctcagcct     2460

cctaagtagc tgggactaca ggtatgtgcc accacgcctg gctaattttt atatttttag     2520

tagagacggg gtttcaccat gttgtccagg ctggtctcaa actcctgacc tcaggtgatc     2580

tgcccacctc tgcctcccaa agtgctggga ttacaggcat gagccaccat gcctggccat     2640

ttcttacact tttgtatgac atgcctattg caagcttgcg tgcctctgtc ccatgttatt     2700

ttactctggg atttaggtgg agggagcagc ttctatttgg aacattggcc atcgcatggc     2760

aaatgggtat ctgtcacttc tgctcctatt tagttggttc tactataacc tttagagcaa     2820

atcctgcagc caagccaggc atcaataggg cagaaaagta tattctgtaa ataggggtga     2880

ggagaagata tttctgaaca atagtctact gcagtaccaa attgcttttc aaagtggctg     2940

ttctaatgta ctcccgtcag tcatataagt gtcatgtaag tatcccattg atccacatcc     3000

ttgctaccct ctggtactat caggtgccct taattttgcc aagccagtgg gtatagaatg     3060

agatctcact gtggtcttag tttgcatttg cttggttact gatgagcacc ttgtcaaata     3120

tttatatacc atttgtgttt atttttttaa ataaaatgct tgctcatgct tttttgccca     3180

tttgcaaaaa aacttggggc cgggtgcagt ggctcatgcc tgtagtccca gctctttggg     3240

aggccaaggt gggcagatcg cttgagccca ggagttcgag accagccttg gcaacatggc     3300

gaaaccctgt ctttacaaaa aatacaaaaa ttagccgggt gtggtggtgt gcacctgaag     3360

tcccagctac tcagtaggtt cgctttgagc ctgggaggca gaggttgcag tgagctggga     3420

ccgcatcact acacttcagc ctgggcaaca gagaaaaacc ttttctcaga aacaaacaaa     3480

cccaaatgtg gttgtttgtc ctgattccta aaaggtcttt atgtattcta gataataatc     3540

tttggtcagt tatatgtgtt aaaaaatatc ttctttgtgg ccaggcacgg tagctcacac     3600

ctgtaatccc agcactttgc ggggctgagg tgggtggatc atctgaggtc aagagttcaa     3660

gatcagcctg gccaacacag tgaaacccca tctctactaa acatgtacaa aacttagctg     3720

ggtatggtgg cgggtgcctg taaccccagc tgctccagag gctgtggcag aagaatcgct     3780

tgaacccagg aggcagaggt tgcagcgagc caagattgtg ccattgcact ccagactggg     3840

tgacaagagt gaaattctgc ctatctatct atctatctat ctatatctat atatatatat     3900

atatatatcc tttgtaattt atttttccct ttttaaaatt ttttataaaa ttctttttta     3960

tttttatttt tagcagaggt gaggtttctg aggtttcatt atgttgccca ggctggtctt     4020

gaactcctga gctcaagtga tcctcccacc tcagccttcc aaagtgctgg aattgcagac     4080

atgagccacc gcgcccctcc tgtttttctc taattaatgg tgtctttctt tgtctttctg     4140

gtaataagca aaaagttctt catttgattt ggttaaattt ataactgttt tctcatatgg     4200

ttaacatttt ttcttgcctg gctaaagaaa tccttttctg cccaatacta taaagaggtt     4260

tgcccacatt ttattccaaa agttttaagt tttgtctttc atcttgaagt ctaatgtatc     4320

aggaactggc ttttgtgcct gttgggaggt agtgatccaa ttccatgtct tgcatgtagg     4380

taaccactgg tccctgcgcc atgtattcaa tacgtcgtct ttctcctgcg ggtctgcaat     4440

ctcacctacc atccatcaag tttccatagg gccatgggtc tgcttctggg ctccctgttc     4500

tgttccattg tcaatttgtc tatcctgtgc cagtatcaca ctgtgtttat tacaatagct     4560

ttgtaacagc tctcgatatc cggtaggaca tctccctcca ccttcttttt ctacttcaga     4620

agtgtcttag ctaggtcagg cacggtggct cacgcctgta atcccagcac tttgggaggc     4680

cgacgcggat ggatcacctg aggtcaggag ttttgagaca gcctggccaa catggtgaaa     4740

ccccatctct actaaaaaat acaaaaatta gtcaggcatg gtggcatgtg cctgtaatcc     4800

cagctatttg ggaggctgag gccggagaat tgcttgaacc cggggggcgg aggttgcagt     4860

gagccgagat cgtaccattg cactccagcc tgggtgacag agcgaaactc tgtctcagga     4920

aaaaaaagaa aagagatgtc ttggttattc ttggttcttt attattcaat ataaatttta     4980

gaagctgaat ttgaaaagat ttggattgga atttcattaa atctacaggt caatttaggg     5040

agagttgata attttacaga attgagtcat ctggtgttcc aataagaata agagaacaat     5100

tattggctgt acaattcttg ccaaatagta ggcaaagcaa agcttaggaa gtatactggt     5160

gccatttcag gaacaaagct aggtgcgaat atttttgtct ttctgaatca tgatgctgta     5220

agttctaaag tgatttctcc tcttggcttt ggacacatgg tgtttaatta cctactgctg     5280

actatccaca aacagaaaga gactggtcat gccccacagg gttggggtat ccaagataat     5340

ggagcgaggc tctcatgtgt cctaggttac acaccgaaaa tccacagttt attctgtgaa     5400

gaaaggaggc tatgtttatg atacagactg tgatattttt atcatagcct attctggtat     5460

catgtgcaaa agctataaat gaaaaacaca ggaacttggc atgtgagtca ttgctccccc     5520

taaatgacaa ttaataagga aggaacattg agacagaata aaatgatccc cttctgggtt     5580

taatttagaa agttccataa ttaggtttaa tagaaataaa tgtaaatttc tatgattaaa     5640

aataaattag cacatttagg gatacacaaa ttataaatca ttttctaaat gctaaaaaca     5700

agctcaggtt tttttcagaa gaaagtttta attttttttc tttagtggaa gatatcactc     5760

tgacggaaag ttttgatgtg aggggcggat gactataaag tgggcatctt cccccacagg     5820

aagatgtttc catctgtggg tgagaggtgc ccaccgcagc tagggcaggt tacatgtgcc     5880

ctgtgtgtgg taggacttgg agagtgatct ttatcaacgt ttttatttaa aagactatct     5940

aataaaacac aaaactatga tgttcacagg aaaaaaagaa taagaaaaaa agaaaaaaaa     6000

a                                                                     6001


<210>  54
<211>  255
<212>  PRT
<213>  Homo sapiens

<400>  54

Met Gly Asn Ser Cys Tyr Asn Ile Val Ala Thr Leu Leu Leu Val Leu 
1               5                   10                  15      


Asn Phe Glu Arg Thr Arg Ser Leu Gln Asp Pro Cys Ser Asn Cys Pro 
            20                  25                  30          


Ala Gly Thr Phe Cys Asp Asn Asn Arg Asn Gln Ile Cys Ser Pro Cys 
        35                  40                  45              


Pro Pro Asn Ser Phe Ser Ser Ala Gly Gly Gln Arg Thr Cys Asp Ile 
    50                  55                  60                  


Cys Arg Gln Cys Lys Gly Val Phe Arg Thr Arg Lys Glu Cys Ser Ser 
65                  70                  75                  80  


Thr Ser Asn Ala Glu Cys Asp Cys Thr Pro Gly Phe His Cys Leu Gly 
                85                  90                  95      


Ala Gly Cys Ser Met Cys Glu Gln Asp Cys Lys Gln Gly Gln Glu Leu 
            100                 105                 110         


Thr Lys Lys Gly Cys Lys Asp Cys Cys Phe Gly Thr Phe Asn Asp Gln 
        115                 120                 125             


Lys Arg Gly Ile Cys Arg Pro Trp Thr Asn Cys Ser Leu Asp Gly Lys 
    130                 135                 140                 


Ser Val Leu Val Asn Gly Thr Lys Glu Arg Asp Val Val Cys Gly Pro 
145                 150                 155                 160 


Ser Pro Ala Asp Leu Ser Pro Gly Ala Ser Ser Val Thr Pro Pro Ala 
                165                 170                 175     


Pro Ala Arg Glu Pro Gly His Ser Pro Gln Ile Ile Ser Phe Phe Leu 
            180                 185                 190         


Ala Leu Thr Ser Thr Ala Leu Leu Phe Leu Leu Phe Phe Leu Thr Leu 
        195                 200                 205             


Arg Phe Ser Val Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe 
    210                 215                 220                 


Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly 
225                 230                 235                 240 


Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu 
                245                 250                 255 


<210>  55
<211>  2137
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  4-1BB mRNA sequence of the humanized mouse

<400>  55
ttcctgaaat tcaggtgctg caggcagccc tcagcacaga gagctgacag ggaccctggg       60

tcaggggttc tgagttccag ctgccactat tcttcttcac ctttggtgtc ctgtgcatgt      120

gacatttcgc catgggaaac agctgttaca acatagtagc cactctgttg ctggtcctca      180

actttgagag gacaagatca ttgcaggatc cttgtagtaa ctgcccagct ggtacattct      240

gtgataataa caggaatcag atttgcagtc cctgtcctcc aaatagtttc tccagcgcag      300

gtggacaaag gacctgtgac atatgcaggc agtgtaaagg tgttttcagg accaggaagg      360

agtgttcctc caccagcaat gcagagtgtg actgcactcc agggtttcac tgcctggggg      420

caggatgcag catgtgtgaa caggattgta aacaaggtca agaactgaca aaaaaaggtt      480

gtaaagactg ttgctttggg acatttaacg atcagaaacg tggcatctgt cgaccctgga      540

caaactgttc tttggatgga aagtctgtgc ttgtgaatgg gacgaaggag agggacgtgg      600

tctgtggacc atctccagcc gacctctctc cgggagcatc ctctgtgacc ccgcctgccc      660

ctgcgagaga gccaggacac tctttgcagg tccttacctt gttcctggcg ctgacatcgg      720

ctttgctgct ggccctgatc ttcattactc tcctgttctc tgtgctcaaa tggatcagga      780

aaaaattccc ccacatattc aagcaaccat ttaagaagac cactggagca gctcaagagg      840

aagatgcttg tagctgccga tgtccacagg aagaagaagg aggaggagga ggctatgagc      900

tgtgatgtac tatcctagga gatgtgtggg ccgaaaccga gaagcactag gaccccacca      960

tcctgtggaa cagcacaagc aaccccacca ccctgttctt acacatcatc ctagatgatg     1020

tgtgggcgcg cacctcatcc aagtctcttc taacgctaac atatttgtct ttaccttttt     1080

taaatctttt tttaaattta aattttatgt gtgtgagtgt tttgcctgcc tgtatgcaca     1140

cgtgtgtgtg tgtgtgtgtg tgacactcct gatgcctgag gaggtcagaa gagaaagggt     1200

tggttccata agaactggag ttatggatgg ctgtgagcct ttgtgtgggt gctaggaatc     1260

aaacctgggt cctctacaag ggcagccagt gctcttaacc actgagtcag ctttccagcc     1320

ctgccctgga cagtttttaa aatttaactt aatttttttt tttttttact taagccctta     1380

acatttttaa taggactgtg ggaagatcaa tttctagatt ctccttaaca atatacatca     1440

tatacatata cacatacata tacatataca tatatattct gagaaaatga cagtttcagt     1500

tggatctcat agaccaatgg tccagttaaa ataactgtaa aatcagtgtg tgtgtgtgtg     1560

tgtgtgtgtg tgtgcaaata tgatgcatga caatagccat aagatgcagt atattaccct     1620

atcccatttt cctttggttt ctcactcact ataataacac ctccactgtc tgaaggggga     1680

gacccatgca tccctgtctg gaggaagcct gacagatttt gaggggaatc ttcagagcag     1740

ttcaagggcc tgcttctcct gtttcctctg tgtcaggctt ttcaataaaa aggccgttta     1800

ggaaagggac aaagcactgt gaggtgggga acacctgtga actcacagta ggaacgcggc     1860

cttccagtcc accatgggca gacatggctg ccgcttgcct ctgcatgact cctggacagc     1920

tcaagagctg agaatggttg ttacttttct ttattttgag acagcacctc cctctgtagt     1980

gctggctggc ctggaagtca cagaaatcct cctgcctctg cttccagagt actgggtctt     2040

aaactgttca ccacgtctcc cctccccaac ccccaaacta gcctttccat ttttaaaagc     2100

cagctaaaaa tattaaagtt gtgctcttac aaaagtc                              2137


<210>  56
<211>  257
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  4-1BB protein expressed by the humanized mouse

<400>  56

Met Gly Asn Ser Cys Tyr Asn Ile Val Ala Thr Leu Leu Leu Val Leu 
1               5                   10                  15      


Asn Phe Glu Arg Thr Arg Ser Leu Gln Asp Pro Cys Ser Asn Cys Pro 
            20                  25                  30          


Ala Gly Thr Phe Cys Asp Asn Asn Arg Asn Gln Ile Cys Ser Pro Cys 
        35                  40                  45              


Pro Pro Asn Ser Phe Ser Ser Ala Gly Gly Gln Arg Thr Cys Asp Ile 
    50                  55                  60                  


Cys Arg Gln Cys Lys Gly Val Phe Arg Thr Arg Lys Glu Cys Ser Ser 
65                  70                  75                  80  


Thr Ser Asn Ala Glu Cys Asp Cys Thr Pro Gly Phe His Cys Leu Gly 
                85                  90                  95      


Ala Gly Cys Ser Met Cys Glu Gln Asp Cys Lys Gln Gly Gln Glu Leu 
            100                 105                 110         


Thr Lys Lys Gly Cys Lys Asp Cys Cys Phe Gly Thr Phe Asn Asp Gln 
        115                 120                 125             


Lys Arg Gly Ile Cys Arg Pro Trp Thr Asn Cys Ser Leu Asp Gly Lys 
    130                 135                 140                 


Ser Val Leu Val Asn Gly Thr Lys Glu Arg Asp Val Val Cys Gly Pro 
145                 150                 155                 160 


Ser Pro Ala Asp Leu Ser Pro Gly Ala Ser Ser Val Thr Pro Pro Ala 
                165                 170                 175     


Pro Ala Arg Glu Pro Gly His Ser Leu Gln Val Leu Thr Leu Phe Leu 
            180                 185                 190         


Ala Leu Thr Ser Ala Leu Leu Leu Ala Leu Ile Phe Ile Thr Leu Leu 
        195                 200                 205             


Phe Ser Val Leu Lys Trp Ile Arg Lys Lys Phe Pro His Ile Phe Lys 
    210                 215                 220                 


Gln Pro Phe Lys Lys Thr Thr Gly Ala Ala Gln Glu Glu Asp Ala Cys 
225                 230                 235                 240 


Ser Cys Arg Cys Pro Gln Glu Glu Glu Gly Gly Gly Gly Gly Tyr Glu 
                245                 250                 255     


Leu 
    


<210>  57
<211>  552
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  4-1BB mRNA sequence comprised by the humanized mouse

<400>  57
atgggaaaca gctgttacaa catagtagcc actctgttgc tggtcctcaa ctttgagagg       60

acaagatcat tgcaggatcc ttgtagtaac tgcccagctg gtacattctg tgataataac      120

aggaatcaga tttgcagtcc ctgtcctcca aatagtttct ccagcgcagg tggacaaagg      180

acctgtgaca tatgcaggca gtgtaaaggt gttttcagga ccaggaagga gtgttcctcc      240

accagcaatg cagagtgtga ctgcactcca gggtttcact gcctgggggc aggatgcagc      300

atgtgtgaac aggattgtaa acaaggtcaa gaactgacaa aaaaaggttg taaagactgt      360

tgctttggga catttaacga tcagaaacgt ggcatctgtc gaccctggac aaactgttct      420

ttggatggaa agtctgtgct tgtgaatggg acgaaggaga gggacgtggt ctgtggacca      480

tctccagccg acctctctcc gggagcatcc tctgtgaccc cgcctgcccc tgcgagagag      540

ccaggacact ct                                                          552


<210>  58
<211>  308
<212>  PRT
<213>  Rattus norvegicus

<400>  58

Met Asp Gln His Ala Leu Asp Val Gly Gly Thr Val Asp Ala Gly His 
1               5                   10                  15      


Pro Pro Gly Thr Ala Gln Pro Pro Asp Ala Ala Phe Leu Arg Asp Thr 
            20                  25                  30          


Gly Leu Pro Ser Asp Ala Ala Phe Leu Val Asp Thr Val Arg Leu Thr 
        35                  40                  45              


Glu Ala Ala Leu Pro Thr Asp Ala Ala Cys Pro Ala Val Asn Val Arg 
    50                  55                  60                  


Asp Pro Glu Ala Ala Trp Pro Pro Ala Leu Asn Phe Cys Ser Arg His 
65                  70                  75                  80  


Pro Arg Leu Tyr Cys Leu Gly Gly Leu Val Leu Leu Leu Leu Val Ala 
                85                  90                  95      


Cys Val Pro Ile Phe Ile Arg Ile Leu Pro Gln Pro Ala Leu Thr Ile 
            100                 105                 110         


Thr Thr Ser Pro Asp Leu Asp Thr Gly Glu Asn Thr Ala Asp Gln Val 
        115                 120                 125             


Thr Pro Val Ser His Ile Gly Cys Ala Asn Thr Thr Gln Gln Gly Phe 
    130                 135                 140                 


Pro Val Phe Ala Lys Leu Leu Ala Lys Asn Gln Ala Ser Leu Ser Asn 
145                 150                 155                 160 


Thr Thr Leu Asn Trp His Ser Gln Glu Gly Ala Gly Ser Ser Tyr Leu 
                165                 170                 175     


Ser Arg Gly Leu Arg Tyr Glu Glu Asp Lys Lys Glu Leu Val Val Asp 
            180                 185                 190         


Ser Pro Gly Leu Tyr Tyr Val Phe Leu Glu Leu Lys Leu Ser Pro Thr 
        195                 200                 205             


Ser Ile Asn Thr Gly Arg Lys Val Gln Gly Trp Val Ser Leu Val Leu 
    210                 215                 220                 


Gln Ala Lys Pro Gln Val Asp His Leu Asp Ser Leu Ala Leu Thr Val 
225                 230                 235                 240 


Glu Leu Phe Pro Cys Ser Met Glu Asp Lys Leu Val Asp Arg Ser Trp 
                245                 250                 255     


Asn Arg Leu Leu Arg Leu Lys Ala Gly His Arg Leu Ser Val Asp Leu 
            260                 265                 270         


Arg Ala Tyr Leu His Gly Ala Gln Asp Ala Tyr Arg Asp Trp Glu Leu 
        275                 280                 285             


Ser His Ala Asn Thr Thr Ser Phe Gly Leu Phe Leu Val Lys Pro Asp 
    290                 295                 300                 


Pro Pro Gln Gly 
305             


<210>  59
<211>  258
<212>  PRT
<213>  Rattus norvegicus

<400>  59

Met Gly Ser Ser Cys Tyr Asn Met Val Val Thr Val Leu Leu Val Val 
1               5                   10                  15      


Gly Thr Glu Glu Val Arg Ala Thr Arg Asn Pro Cys Asp Ser Cys Glu 
            20                  25                  30          


Ala Gly Thr Phe Cys Ser Lys Tyr Pro Pro Val Cys Thr Ser Cys Pro 
        35                  40                  45              


Pro Ser Thr Tyr Ser Ser Thr Gly Gly Gln Pro Asn Cys Asp Ile Cys 
    50                  55                  60                  


Arg Val Cys Gln Gly Tyr Phe Arg Phe Lys Lys Pro Cys Ser Ser Thr 
65                  70                  75                  80  


His Asn Ala Glu Cys Glu Cys Val Glu Gly Phe His Cys Leu Gly Pro 
                85                  90                  95      


Lys Cys Thr Arg Cys Glu Lys Asp Cys Arg Pro Gly Gln Glu Leu Thr 
            100                 105                 110         


Glu Gln Gly Cys Lys Asn Cys Gly Leu Gly Thr Phe Asn Asp Gln Asp 
        115                 120                 125             


Gly Ala Gly Val Cys Arg Pro Trp Thr Asn Cys Ser Leu Asp Gly Arg 
    130                 135                 140                 


Ser Val Leu Lys Asn Gly Thr Lys Glu Lys Asp Val Val Cys Gly Pro 
145                 150                 155                 160 


Pro Val Val Ser Leu Ser Pro Ser Thr Thr Pro Ser Ala Val Thr Thr 
                165                 170                 175     


Pro Glu Arg Glu Ser Gly Glu Arg Pro Leu Gln Val Leu Thr Leu Phe 
            180                 185                 190         


Leu Ala Leu Thr Leu Ala Leu Leu Leu Phe Leu Ile Phe Ile Ile Leu 
        195                 200                 205             


Trp Phe Ser Val Pro Lys Trp Leu Arg Lys Lys Phe Pro His Ile Phe 
    210                 215                 220                 


Lys Gln Pro Phe Lys Lys Ala Val Arg Thr Ala Gln Glu Glu Asp Ala 
225                 230                 235                 240 


Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Gly Gly Ser Tyr 
                245                 250                 255     


Glu Leu 
        


