                         SEQUENCE LISTING

<110>  Seattle Children's Research Institute d/b/a Seattle Children's 
       Research Institute
 
<120>  GENE EDITING FOR EXPRESSION OF FUNCTIONAL FACTOR VIII FOR THE 
       TREATMENT OF HEMOPHILIA

<130>  S281-0031PCT / SCRI.375WO

<150>  US 63/187,200
<151>  2021-05-11

<150>  US 63/331,591
<151>  2022-04-15

<160>  17    

<170>  PatentIn version 3.5

<210>  1
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA sequence targeting wild type mF8 exon 1

<400>  1
gccatcagaa gatactacct                                                   20


<210>  2
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA targeting mutant mF8 exon 1

<400>  2
atcagaagat actaccttgg                                                   20


<210>  3
<211>  56
<212>  DNA
<213>  Mus musculus

<400>  3
atcagaagat actaccttgg tgcagtggaa ttgtcctgga actatattca gagtga           56


<210>  4
<211>  51
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  NSG HemA mouse mutant mF8 exon 1

<400>  4
atcagaagat actaccttgg tggaattgtc ctggaactat attcagagtg a                51


<210>  5
<211>  62
<212>  DNA
<213>  Mus musculus

<400>  5
agtgccatca gaagatacta ccttggtgca gtggaattgt cctggaacta tattcagagt       60

ga                                                                      62


<210>  6
<211>  57
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  NSG HemA mouse mutant mF8 exon 1

<400>  6
agtgccatca gaagatacta ccttggtgga attgtcctgg aactatattc agagtga          57


<210>  7
<211>  46
<212>  PRT
<213>  Mus musculus

<400>  7

Met Gln Ile Ala Leu Phe Ala Cys Phe Phe Leu Ser Phe Leu Phe Asn 
1               5                   10                  15      


Phe Cys Ser Ser Ala Ile Arg Arg Tyr Tyr Leu Gly Ala Val Glu Leu 
            20                  25                  30          


Ser Trp Asn Tyr Ile Gln Ser Asp Leu Leu Ser Val Leu His 
        35                  40                  45      


<210>  8
<211>  37
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Mutant Factor VIII amino acids

<400>  8

Met Gln Ile Ala Leu Phe Ala Cys Phe Phe Leu Ser Phe Leu Phe Asn 
1               5                   10                  15      


Phe Cys Ser Ser Ala Ile Arg Arg Tyr Tyr Leu Gly Gly Ile Val Leu 
            20                  25                  30          


Glu Leu Tyr Ser Glu 
        35          


<210>  9
<211>  45
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Indel repair Factor VIII amino acids; +2 repair


<220>
<221>  misc_feature
<222>  (29)..(29)
<223>  Xaa can be any naturally occurring amino acid

<400>  9

Met Gln Ile Ala Leu Phe Ala Cys Phe Phe Leu Ser Phe Leu Phe Asn 
1               5                   10                  15      


Phe Cys Ser Ser Ala Ile Arg Arg Tyr Tyr Leu Gly Xaa Glu Leu Ser 
            20                  25                  30          


Trp Asn Tyr Ile Gln Ser Asp Leu Leu Ser Val Leu His 
        35                  40                  45  


<210>  10
<211>  44
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Indel repair Factor VIII amino acids; -1 repair

<400>  10

Met Gln Ile Ala Leu Phe Ala Cys Phe Phe Leu Ser Phe Leu Phe Asn 
1               5                   10                  15      


Phe Cys Ser Ser Ala Ile Arg Arg Tyr Tyr Leu Gly Glu Leu Ser Trp 
            20                  25                  30          


Asn Tyr Ile Gln Ser Asp Leu Leu Ser Val Leu His 
        35                  40                  


<210>  11
<211>  11703
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Cas9 nuclease targeting mF8 guide RNA

<400>  11
ttaatgtagt cttatgcaat actcttgtag tcttgcaaca tggtaacgat gagttagcaa       60

catgccttac aaggagagaa aaagcaccgt gcatgccgat tggtggaagt aaggtggtac      120

gatcgtgcct tattaggaag gcaacagacg ggtctgacat ggattggacg aaccactgaa      180

ttgccgcatt gcagagatat tgtatttaag tgcctagctc gatacataaa cgggtctctc      240

tggttagacc agatctgagc ctgggagctc tctggctaac tagggaaccc actgcttaag      300

cctcaataaa gcttgccttg agtgcttcaa gtagtgtgtg cccgtctgtt gtgtgactct      360

ggtaactaga gatccctcag acccttttag tcagtgtgga aaatctctag cagtggcgcc      420

cgaacaggga cttgaaagcg aaagggaaac cagaggagct ctctcgacgc aggactcggc      480

ttgctgaagc gcgcacggca agaggcgagg ggcggcgact ggtgagtacg ccaaaaattt      540

tgactagcgg aggctagaag gagagagatg ggtgcgagag cgtcagtatt aagcggggga      600

gaattagatc gcgatgggaa aaaattcggt taaggccagg gggaaagaaa aaatataaat      660

taaaacatat agtatgggca agcagggagc tagaacgatt cgcagttaat cctggcctgt      720

tagaaacatc agaaggctgt agacaaatac tgggacagct acaaccatcc cttcagacag      780

gatcagaaga acttagatca ttatataata cagtagcaac cctctattgt gtgcatcaaa      840

ggatagagat aaaagacacc aaggaagctt tagacaagat agaggaagag caaaacaaaa      900

gtaagaccac cgcacagcaa gcggccgctg atcttcagac ctggaggagg agatatgagg      960

gacaattgga gaagtgaatt atataaatat aaagtagtaa aaattgaacc attaggagta     1020

gcacccacca aggcaaagag aagagtggtg cagagagaaa aaagagcagt gggaatagga     1080

gctttgttcc ttgggttctt gggagcagca ggaagcacta tgggcgcagc gtcaatgacg     1140

ctgacggtac aggccagaca attattgtct ggtatagtgc agcagcagaa caatttgctg     1200

agggctattg aggcgcaaca gcatctgttg caactcacag tctggggcat caagcagctc     1260

caggcaagaa tcctggctgt ggaaagatac ctaaaggatc aacagctcct ggggatttgg     1320

ggttgctctg gaaaactcat ttgcaccact gctgtgcctt ggaatgctag ttggagtaat     1380

aaatctctgg aacagatttg gaatcacacg acctggatgg agtgggacag agaaattaac     1440

aattacacaa gcttaataca ctccttaatt gaagaatcgc aaaaccagca agaaaagaat     1500

gaacaagaat tattggaatt agataaatgg gcaagtttgt ggaattggtt taacataaca     1560

aattggctgt ggtatataaa attattcata atgatagtag gaggcttggt aggtttaaga     1620

atagtttttg ctgtactttc tatagtgaat agagttaggc agggatattc accattatcg     1680

tttcagaccc acctcccaac cccgagggga cccagagagg gcctatttcc catgattcct     1740

tcatatttgc atatacgata caaggctgtt agagagataa ttagaattaa tttgactgta     1800

aacacaaaga tattagtaca aaatacgtga cgtagaaagt aataatttct tgggtagttt     1860

gcagttttaa aattatgttt taaaatggac tatcatatgc ttaccgtaac ttgaaagtat     1920

ttcgatttct tggctttata tatcttgtgg aaaggacgaa acaccgccat cagaagatac     1980

tacctgtttt agagctagaa atagcaagtt aaaataaggc tagtccgtta tcaacttgaa     2040

aaagtggcac cgagtcggtg cttttttgaa ttctagatct tgagacaaat ggcagtattc     2100

atccacaatt ttaaaagaaa aggggggatt ggggggtaca gtgcagggga aagaatagta     2160

gacataatag caacagacat acaaactaaa gaattacaaa aacaaattac aaaaattcaa     2220

aattttcggg tttattacag ggacagcaga gatccacttt ggcgccggct cgagtggctc     2280

cggtgcccgt cagtgggcag agcgcacatc gcccacagtc cccgagaagt tggggggagg     2340

ggtcggcaat tgaaccggtg cctagagaag gtggcgcggg gtaaactggg aaagtgatgt     2400

cgtgtactgg ctccgccttt ttcccgaggg tgggggagaa ccgtatataa gtgcagtagt     2460

cgccgtgaac gttctttttc gcaacgggtt tgccgccaga acacaggtgt cgtgacgcgg     2520

gatccgccac catggattac aaagacgatg acgataagat ggccccaaag aagaagcgga     2580

aggtcggtat ccacggagtc ccagcagccg acaagaagta cagcatcggc ctggacatcg     2640

gcaccaactc tgtgggctgg gccgtgatca ccgacgagta caaggtgccc agcaagaaat     2700

tcaaggtgct gggcaacacc gaccggcaca gcatcaagaa gaacctgatc ggagccctgc     2760

tgttcgacag cggcgaaaca gccgaggcca cccggctgaa gagaaccgcc agaagaagat     2820

acaccagacg gaagaaccgg atctgctatc tgcaagagat cttcagcaac gagatggcca     2880

aggtggacga cagcttcttc cacagactgg aagagtcctt cctggtggaa gaggataaga     2940

agcacgagcg gcaccccatc ttcggcaaca tcgtggacga ggtggcctac cacgagaagt     3000

accccaccat ctaccacctg agaaagaaac tggtggacag caccgacaag gccgacctgc     3060

ggctgatcta tctggccctg gcccacatga tcaagttccg gggccacttc ctgatcgagg     3120

gcgacctgaa ccccgacaac agcgacgtgg acaagctgtt catccagctg gtgcagacct     3180

acaaccagct gttcgaggaa aaccccatca acgccagcgg cgtggacgcc aaggccatcc     3240

tgtctgccag actgagcaag agcagacggc tggaaaatct gatcgcccag ctgcccggcg     3300

agaagaagaa tggcctgttc ggaaacctga ttgccctgag cctgggcctg acccccaact     3360

tcaagagcaa cttcgacctg gccgaggatg ccaaactgca gctgagcaag gacacctacg     3420

acgacgacct ggacaacctg ctggcccaga tcggcgacca gtacgccgac ctgtttctgg     3480

ccgccaagaa cctgtccgac gccatcctgc tgagcgacat cctgagagtg aacaccgaga     3540

tcaccaaggc ccccctgagc gcctctatga tcaagagata cgacgagcac caccaggacc     3600

tgaccctgct gaaagctctc gtgcggcagc agctgcctga gaagtacaaa gagattttct     3660

tcgaccagag caagaacggc tacgccggct acattgacgg cggagccagc caggaagagt     3720

tctacaagtt catcaagccc atcctggaaa agatggacgg caccgaggaa ctgctcgtga     3780

agctgaacag agaggacctg ctgcggaagc agcggacctt cgacaacggc agcatccccc     3840

accagatcca cctgggagag ctgcacgcca ttctgcggcg gcaggaagat ttttacccat     3900

tcctgaagga caaccgggaa aagatcgaga agatcctgac cttccgcatc ccctactacg     3960

tgggccctct ggccagggga aacagcagat tcgcctggat gaccagaaag agcgaggaaa     4020

ccatcacccc ctggaacttc gaggaagtgg tggacaaggg cgcttccgcc cagagcttca     4080

tcgagcggat gaccaacttc gataagaacc tgcccaacga gaaggtgctg cccaagcaca     4140

gcctgctgta cgagtacttc accgtgtata acgagctgac caaagtgaaa tacgtgaccg     4200

agggaatgag aaagcccgcc ttcctgagcg gcgagcagaa aaaggccatc gtggacctgc     4260

tgttcaagac caaccggaaa gtgaccgtga agcagctgaa agaggactac ttcaagaaaa     4320

tcgagtgctt cgactccgtg gaaatctccg gcgtggaaga tcggttcaac gcctccctgg     4380

gcacatacca cgatctgctg aaaattatca aggacaagga cttcctggac aatgaggaaa     4440

acgaggacat tctggaagat atcgtgctga ccctgacact gtttgaggac agagagatga     4500

tcgaggaacg gctgaaaacc tatgcccacc tgttcgacga caaagtgatg aagcagctga     4560

agcggcggag atacaccggc tggggcaggc tgagccggaa gctgatcaac ggcatccggg     4620

acaagcagtc cggcaagaca atcctggatt tcctgaagtc cgacggcttc gccaacagaa     4680

acttcatgca gctgatccac gacgacagcc tgacctttaa agaggacatc cagaaagccc     4740

aggtgtccgg ccagggcgat agcctgcacg agcacattgc caatctggcc ggcagccccg     4800

ccattaagaa gggcatcctg cagacagtga aggtggtgga cgagctcgtg aaagtgatgg     4860

gccggcacaa gcccgagaac atcgtgatcg aaatggccag agagaaccag accacccaga     4920

agggacagaa gaacagccgc gagagaatga agcggatcga agagggcatc aaagagctgg     4980

gcagccagat cctgaaagaa caccccgtgg aaaacaccca gctgcagaac gagaagctgt     5040

acctgtacta cctgcagaat gggcgggata tgtacgtgga ccaggaactg gacatcaacc     5100

ggctgtccga ctacgatgtg gaccatatcg tgcctcagag ctttctgaag gacgactcca     5160

tcgacaacaa ggtgctgacc agaagcgaca agaaccgggg caagagcgac aacgtgccct     5220

ccgaagaggt cgtgaagaag atgaagaact actggcggca gctgctgaac gccaagctga     5280

ttacccagag aaagttcgac aatctgacca aggccgagag aggcggcctg agcgaactgg     5340

ataaggccgg cttcatcaag agacagctgg tggaaacccg gcagatcaca aagcacgtgg     5400

cacagatcct ggactcccgg atgaacacta agtacgacga gaatgacaag ctgatccggg     5460

aagtgaaagt gatcaccctg aagtccaagc tggtgtccga tttccggaag gatttccagt     5520

tttacaaagt gcgcgagatc aacaactacc accacgccca cgacgcctac ctgaacgccg     5580

tcgtgggaac cgccctgatc aaaaagtacc ctaagctgga aagcgagttc gtgtacggcg     5640

actacaaggt gtacgacgtg cggaagatga tcgccaagag cgagcaggaa atcggcaagg     5700

ctaccgccaa gtacttcttc tacagcaaca tcatgaactt tttcaagacc gagattaccc     5760

tggccaacgg cgagatccgg aagcggcctc tgatcgagac aaacggcgaa accggggaga     5820

tcgtgtggga taagggccgg gattttgcca ccgtgcggaa agtgctgagc atgccccaag     5880

tgaatatcgt gaaaaagacc gaggtgcaga caggcggctt cagcaaagag tctatcctgc     5940

ccaagaggaa cagcgataag ctgatcgcca gaaagaagga ctgggaccct aagaagtacg     6000

gcggcttcga cagccccacc gtggcctatt ctgtgctggt ggtggccaaa gtggaaaagg     6060

gcaagtccaa gaaactgaag agtgtgaaag agctgctggg gatcaccatc atggaaagaa     6120

gcagcttcga gaagaatccc atcgactttc tggaagccaa gggctacaaa gaagtgaaaa     6180

aggacctgat catcaagctg cctaagtact ccctgttcga gctggaaaac ggccggaaga     6240

gaatgctggc ctctgccggc gaactgcaga agggaaacga actggccctg ccctccaaat     6300

atgtgaactt cctgtacctg gccagccact atgagaagct gaagggctcc cccgaggata     6360

atgagcagaa acagctgttt gtggaacagc acaagcacta cctggacgag atcatcgagc     6420

agatcagcga gttctccaag agagtgatcc tggccgacgc taatctggac aaagtgctgt     6480

ccgcctacaa caagcaccgg gataagccca tcagagagca ggccgagaat atcatccacc     6540

tgtttaccct gaccaatctg ggagcccctg ccgccttcaa gtactttgac accaccatcg     6600

accggaagag gtacaccagc accaaagagg tgctggacgc caccctgatc caccagagca     6660

tcaccggcct gtacgagaca cggatcgacc tgtctcagct gggaggcgac aagcgtcctg     6720

ctgctactaa gaaagctggt caagctaaga aaaagaaagc tagcggcagc ggcgccacca     6780

acttcagcct gctgaagcag gccggcgacg tggaggagaa ccccggcccc atggtgtcta     6840

agggcgaaga gctgattaag gagaacatgc acatgaagct gtatatggag ggcaccgtga     6900

acaaccacca cttcaagtgc acatccgagg gcgaaggcaa gccctacgag ggcacccaga     6960

ccatgagaat caaggtggtc gagggcggcc ctctcccctt cgccttcgac atcctggcta     7020

ccagcttcat gtacggcagc agaaccttca tcaaccacac ccagggcatc cccgacttct     7080

ttaagcagtc cttccctgag ggcttcacat gggagagagt caccacatac gaagacgggg     7140

gcgtgctgac cgctacccag gacaccagcc tccaggacgg ctgcctcatc tacaacgtca     7200

agatcagagg ggtgaacttc ccatccaacg gccctgtgat gcagaagaaa acactcggct     7260

gggaggccaa caccgagatg ctgtaccccg ctgacggcgg cctggaaggc agaagcgaca     7320

tggccctgaa gctcgtgggc gggggccacc tgatctgcaa cttcaagacc acatacagat     7380

ccaagaaacc cgctaagaac ctcaagatgc ccggcgtcta ctatgtggac cacagactgg     7440

aaagaatcaa ggaggccgac aaagagacct acgtcgagca gcacgaggtg gctgtggcca     7500

gatactgcga cctccctagc aaactggggc acaaacttaa ttgaacgcgt taagtcgaca     7560

atcaacctct ggattacaaa atttgtgaaa gattgactgg tattcttaac tatgttgctc     7620

cttttacgct atgtggatac gctgctttaa tgcctttgta tcatgctatt gcttcccgta     7680

tggctttcat tttctcctcc ttgtataaat cctggttgct gtctctttat gaggagttgt     7740

ggcccgttgt caggcaacgt ggcgtggtgt gcactgtgtt tgctgacgca acccccactg     7800

gttggggcat tgccaccacc tgtcagctcc tttccgggac tttcgctttc cccctcccta     7860

ttgccacggc ggaactcatc gccgcctgcc ttgcccgctg ctggacaggg gctcggctgt     7920

tgggcactga caattccgtg gtgttgtcgg ggaaatcatc gtcctttcct tggctgctcg     7980

cctgtgttgc cacctggatt ctgcgcggga cgtccttctg ctacgtccct tcggccctca     8040

atccagcgga ccttccttcc cgcggcctgc tgccggctct gcggcctctt ccgcgtcttc     8100

gccttcgccc tcagacgagt cggatctccc tttgggccgc ctccccgcgt cgactttaag     8160

accaatgact tacaaggcag ctgtagatct tagccacttt ttaaaagaaa aggggggact     8220

ggaagggcta attcactccc aacgaagaca agatctgctt tttgcttgta ctgggtctct     8280

ctggttagac cagatctgag cctgggagct ctctggctaa ctagggaacc cactgcttaa     8340

gcctcaataa agcttgcctt gagtgcttca agtagtgtgt gcccgtctgt tgtgtgactc     8400

tggtaactag agatccctca gaccctttta gtcagtgtgg aaaatctcta gcagtacgta     8460

tagtagttca tgtcatctta ttattcagta tttataactt gcaaagaaat gaatatcaga     8520

gagtgagagg aacttgttta ttgcagctta taatggttac aaataaagca atagcatcac     8580

aaatttcaca aataaagcat ttttttcact gcattctagt tgtggtttgt ccaaactcat     8640

caatgtatct tatcatgtct ggctctagct atcccgcccc taactccgcc catcccgccc     8700

ctaactccgc ccagttccgc ccattctccg ccccatggct gactaatttt ttttatttat     8760

gcagaggccg aggccgcctc ggcctctgag ctattccaga agtagtgagg aggctttttt     8820

ggaggcctag ggacgtaccc aattcgccct atagtgagtc gtattacgcg cgctcactgg     8880

ccgtcgtttt acaacgtcgt gactgggaaa accctggcgt tacccaactt aatcgccttg     8940

cagcacatcc ccctttcgcc agctggcgta atagcgaaga ggcccgcacc gatcgccctt     9000

cccaacagtt gcgcagcctg aatggcgaat gggacgcgcc ctgtagcggc gcattaagcg     9060

cggcgggtgt ggtggttacg cgcagcgtga ccgctacact tgccagcgcc ctagcgcccg     9120

ctcctttcgc tttcttccct tcctttctcg ccacgttcgc cggctttccc cgtcaagctc     9180

taaatcgggg gctcccttta gggttccgat ttagtgcttt acggcacctc gaccccaaaa     9240

aacttgatta gggtgatggt tcacgtagtg ggccatcgcc ctgatagacg gtttttcgcc     9300

ctttgacgtt ggagtccacg ttctttaata gtggactctt gttccaaact ggaacaacac     9360

tcaaccctat ctcggtctat tcttttgatt tataagggat tttgccgatt tcggcctatt     9420

ggttaaaaaa tgagctgatt taacaaaaat ttaacgcgaa ttttaacaaa atattaacgc     9480

ttacaattta ggtggcactt ttcggggaaa tgtgcgcgga acccctattt gtttattttt     9540

ctaaatacat tcaaatatgt atccgctcat gagacaataa ccctgataaa tgcttcaata     9600

atattgaaaa aggaagagta tgagtattca acatttccgt gtcgccctta ttcccttttt     9660

tgcggcattt tgccttcctg tttttgctca cccagaaacg ctggtgaaag taaaagatgc     9720

tgaagatcag ttgggtgcac gagtgggtta catcgaactg gatctcaaca gcggtaagat     9780

ccttgagagt tttcgccccg aagaacgttt tccaatgatg agcactttta aagttctgct     9840

atgtggcgcg gtattatccc gtattgacgc cgggcaagag caactcggtc gccgcataca     9900

ctattctcag aatgacttgg ttgagtactc accagtcaca gaaaagcatc ttacggatgg     9960

catgacagta agagaattat gcagtgctgc cataaccatg agtgataaca ctgcggccaa    10020

cttacttctg acaacgatcg gaggaccgaa ggagctaacc gcttttttgc acaacatggg    10080

ggatcatgta actcgccttg atcgttggga accggagctg aatgaagcca taccaaacga    10140

cgagcgtgac accacgatgc ctgtagcaat ggcaacaacg ttgcgcaaac tattaactgg    10200

cgaactactt actctagctt cccggcaaca attaatagac tggatggagg cggataaagt    10260

tgcaggacca cttctgcgct cggcccttcc ggctggctgg tttattgctg ataaatctgg    10320

agccggtgag cgtgggtctc gcggtatcat tgcagcactg gggccagatg gtaagccctc    10380

ccgtatcgta gttatctaca cgacggggag tcaggcaact atggatgaac gaaatagaca    10440

gatcgctgag ataggtgcct cactgattaa gcattggtaa ctgtcagacc aagtttactc    10500

atatatactt tagattgatt taaaacttca tttttaattt aaaaggatct aggtgaagat    10560

cctttttgat aatctcatga ccaaaatccc ttaacgtgag ttttcgttcc actgagcgtc    10620

agaccccgta gaaaagatca aaggatcttc ttgagatcct ttttttctgc gcgtaatctg    10680

ctgcttgcaa acaaaaaaac caccgctacc agcggtggtt tgtttgccgg atcaagagct    10740

accaactctt tttccgaagg taactggctt cagcagagcg cagataccaa atactgttct    10800

tctagtgtag ccgtagttag gccaccactt caagaactct gtagcaccgc ctacatacct    10860

cgctctgcta atcctgttac cagtggctgc tgccagtggc gataagtcgt gtcttaccgg    10920

gttggactca agacgatagt taccggataa ggcgcagcgg tcgggctgaa cggggggttc    10980

gtgcacacag cccagcttgg agcgaacgac ctacaccgaa ctgagatacc tacagcgtga    11040

gctatgagaa agcgccacgc ttcccgaagg gagaaaggcg gacaggtatc cggtaagcgg    11100

cagggtcgga acaggagagc gcacgaggga gcttccaggg ggaaacgcct ggtatcttta    11160

tagtcctgtc gggtttcgcc acctctgact tgagcgtcga tttttgtgat gctcgtcagg    11220

ggggcggagc ctatggaaaa acgccagcaa cgcggccttt ttacggttcc tggccttttg    11280

ctggcctttt gctcacatgt tctttcctgc gttatcccct gattctgtgg ataaccgtat    11340

taccgccttt gagtgagctg ataccgctcg ccgcagccga acgaccgagc gcagcgagtc    11400

agtgagcgag gaagcggaag agcgcccaat acgcaaaccg cctctccccg cgcgttggcc    11460

gattcattaa tgcagctggc acgacaggtt tcccgactgg aaagcgggca gtgagcgcaa    11520

cgcaattaat gtgagttagc tcactcatta ggcaccccag gctttacact ttatgcttcc    11580

ggctcgtatg ttgtgtggaa ttgtgagcgg ataacaattt cacacaggaa acagctatga    11640

ccatgattac gccaagcgcg caattaaccc tcactaaagg gaacaaaagc tggagctgca    11700

agc                                                                  11703


<210>  12
<211>  11704
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Cas9 nuclease targeting NSGHA mF8 guide RNA

<400>  12
ttaatgtagt cttatgcaat actcttgtag tcttgcaaca tggtaacgat gagttagcaa       60

catgccttac aaggagagaa aaagcaccgt gcatgccgat tggtggaagt aaggtggtac      120

gatcgtgcct tattaggaag gcaacagacg ggtctgacat ggattggacg aaccactgaa      180

ttgccgcatt gcagagatat tgtatttaag tgcctagctc gatacataaa cgggtctctc      240

tggttagacc agatctgagc ctgggagctc tctggctaac tagggaaccc actgcttaag      300

cctcaataaa gcttgccttg agtgcttcaa gtagtgtgtg cccgtctgtt gtgtgactct      360

ggtaactaga gatccctcag acccttttag tcagtgtgga aaatctctag cagtggcgcc      420

cgaacaggga cttgaaagcg aaagggaaac cagaggagct ctctcgacgc aggactcggc      480

ttgctgaagc gcgcacggca agaggcgagg ggcggcgact ggtgagtacg ccaaaaattt      540

tgactagcgg aggctagaag gagagagatg ggtgcgagag cgtcagtatt aagcggggga      600

gaattagatc gcgatgggaa aaaattcggt taaggccagg gggaaagaaa aaatataaat      660

taaaacatat agtatgggca agcagggagc tagaacgatt cgcagttaat cctggcctgt      720

tagaaacatc agaaggctgt agacaaatac tgggacagct acaaccatcc cttcagacag      780

gatcagaaga acttagatca ttatataata cagtagcaac cctctattgt gtgcatcaaa      840

ggatagagat aaaagacacc aaggaagctt tagacaagat agaggaagag caaaacaaaa      900

gtaagaccac cgcacagcaa gcggccgctg atcttcagac ctggaggagg agatatgagg      960

gacaattgga gaagtgaatt atataaatat aaagtagtaa aaattgaacc attaggagta     1020

gcacccacca aggcaaagag aagagtggtg cagagagaaa aaagagcagt gggaatagga     1080

gctttgttcc ttgggttctt gggagcagca ggaagcacta tgggcgcagc gtcaatgacg     1140

ctgacggtac aggccagaca attattgtct ggtatagtgc agcagcagaa caatttgctg     1200

agggctattg aggcgcaaca gcatctgttg caactcacag tctggggcat caagcagctc     1260

caggcaagaa tcctggctgt ggaaagatac ctaaaggatc aacagctcct ggggatttgg     1320

ggttgctctg gaaaactcat ttgcaccact gctgtgcctt ggaatgctag ttggagtaat     1380

aaatctctgg aacagatttg gaatcacacg acctggatgg agtgggacag agaaattaac     1440

aattacacaa gcttaataca ctccttaatt gaagaatcgc aaaaccagca agaaaagaat     1500

gaacaagaat tattggaatt agataaatgg gcaagtttgt ggaattggtt taacataaca     1560

aattggctgt ggtatataaa attattcata atgatagtag gaggcttggt aggtttaaga     1620

atagtttttg ctgtactttc tatagtgaat agagttaggc agggatattc accattatcg     1680

tttcagaccc acctcccaac cccgagggga cccagagagg gcctatttcc catgattcct     1740

tcatatttgc atatacgata caaggctgtt agagagataa ttagaattaa tttgactgta     1800

aacacaaaga tattagtaca aaatacgtga cgtagaaagt aataatttct tgggtagttt     1860

gcagttttaa aattatgttt taaaatggac tatcatatgc ttaccgtaac ttgaaagtat     1920

ttcgatttct tggctttata tatcttgtgg aaaggacgaa acaccgatca gaagatacta     1980

ccttgggttt tagagctaga aatagcaagt taaaataagg ctagtccgtt atcaacttga     2040

aaaagtggca ccgagtcggt gcttttttga attctagatc ttgagacaaa tggcagtatt     2100

catccacaat tttaaaagaa aaggggggat tggggggtac agtgcagggg aaagaatagt     2160

agacataata gcaacagaca tacaaactaa agaattacaa aaacaaatta caaaaattca     2220

aaattttcgg gtttattaca gggacagcag agatccactt tggcgccggc tcgagtggct     2280

ccggtgcccg tcagtgggca gagcgcacat cgcccacagt ccccgagaag ttggggggag     2340

gggtcggcaa ttgaaccggt gcctagagaa ggtggcgcgg ggtaaactgg gaaagtgatg     2400

tcgtgtactg gctccgcctt tttcccgagg gtgggggaga accgtatata agtgcagtag     2460

tcgccgtgaa cgttcttttt cgcaacgggt ttgccgccag aacacaggtg tcgtgacgcg     2520

ggatccgcca ccatggatta caaagacgat gacgataaga tggccccaaa gaagaagcgg     2580

aaggtcggta tccacggagt cccagcagcc gacaagaagt acagcatcgg cctggacatc     2640

ggcaccaact ctgtgggctg ggccgtgatc accgacgagt acaaggtgcc cagcaagaaa     2700

ttcaaggtgc tgggcaacac cgaccggcac agcatcaaga agaacctgat cggagccctg     2760

ctgttcgaca gcggcgaaac agccgaggcc acccggctga agagaaccgc cagaagaaga     2820

tacaccagac ggaagaaccg gatctgctat ctgcaagaga tcttcagcaa cgagatggcc     2880

aaggtggacg acagcttctt ccacagactg gaagagtcct tcctggtgga agaggataag     2940

aagcacgagc ggcaccccat cttcggcaac atcgtggacg aggtggccta ccacgagaag     3000

taccccacca tctaccacct gagaaagaaa ctggtggaca gcaccgacaa ggccgacctg     3060

cggctgatct atctggccct ggcccacatg atcaagttcc ggggccactt cctgatcgag     3120

ggcgacctga accccgacaa cagcgacgtg gacaagctgt tcatccagct ggtgcagacc     3180

tacaaccagc tgttcgagga aaaccccatc aacgccagcg gcgtggacgc caaggccatc     3240

ctgtctgcca gactgagcaa gagcagacgg ctggaaaatc tgatcgccca gctgcccggc     3300

gagaagaaga atggcctgtt cggaaacctg attgccctga gcctgggcct gacccccaac     3360

ttcaagagca acttcgacct ggccgaggat gccaaactgc agctgagcaa ggacacctac     3420

gacgacgacc tggacaacct gctggcccag atcggcgacc agtacgccga cctgtttctg     3480

gccgccaaga acctgtccga cgccatcctg ctgagcgaca tcctgagagt gaacaccgag     3540

atcaccaagg cccccctgag cgcctctatg atcaagagat acgacgagca ccaccaggac     3600

ctgaccctgc tgaaagctct cgtgcggcag cagctgcctg agaagtacaa agagattttc     3660

ttcgaccaga gcaagaacgg ctacgccggc tacattgacg gcggagccag ccaggaagag     3720

ttctacaagt tcatcaagcc catcctggaa aagatggacg gcaccgagga actgctcgtg     3780

aagctgaaca gagaggacct gctgcggaag cagcggacct tcgacaacgg cagcatcccc     3840

caccagatcc acctgggaga gctgcacgcc attctgcggc ggcaggaaga tttttaccca     3900

ttcctgaagg acaaccggga aaagatcgag aagatcctga ccttccgcat cccctactac     3960

gtgggccctc tggccagggg aaacagcaga ttcgcctgga tgaccagaaa gagcgaggaa     4020

accatcaccc cctggaactt cgaggaagtg gtggacaagg gcgcttccgc ccagagcttc     4080

atcgagcgga tgaccaactt cgataagaac ctgcccaacg agaaggtgct gcccaagcac     4140

agcctgctgt acgagtactt caccgtgtat aacgagctga ccaaagtgaa atacgtgacc     4200

gagggaatga gaaagcccgc cttcctgagc ggcgagcaga aaaaggccat cgtggacctg     4260

ctgttcaaga ccaaccggaa agtgaccgtg aagcagctga aagaggacta cttcaagaaa     4320

atcgagtgct tcgactccgt ggaaatctcc ggcgtggaag atcggttcaa cgcctccctg     4380

ggcacatacc acgatctgct gaaaattatc aaggacaagg acttcctgga caatgaggaa     4440

aacgaggaca ttctggaaga tatcgtgctg accctgacac tgtttgagga cagagagatg     4500

atcgaggaac ggctgaaaac ctatgcccac ctgttcgacg acaaagtgat gaagcagctg     4560

aagcggcgga gatacaccgg ctggggcagg ctgagccgga agctgatcaa cggcatccgg     4620

gacaagcagt ccggcaagac aatcctggat ttcctgaagt ccgacggctt cgccaacaga     4680

aacttcatgc agctgatcca cgacgacagc ctgaccttta aagaggacat ccagaaagcc     4740

caggtgtccg gccagggcga tagcctgcac gagcacattg ccaatctggc cggcagcccc     4800

gccattaaga agggcatcct gcagacagtg aaggtggtgg acgagctcgt gaaagtgatg     4860

ggccggcaca agcccgagaa catcgtgatc gaaatggcca gagagaacca gaccacccag     4920

aagggacaga agaacagccg cgagagaatg aagcggatcg aagagggcat caaagagctg     4980

ggcagccaga tcctgaaaga acaccccgtg gaaaacaccc agctgcagaa cgagaagctg     5040

tacctgtact acctgcagaa tgggcgggat atgtacgtgg accaggaact ggacatcaac     5100

cggctgtccg actacgatgt ggaccatatc gtgcctcaga gctttctgaa ggacgactcc     5160

atcgacaaca aggtgctgac cagaagcgac aagaaccggg gcaagagcga caacgtgccc     5220

tccgaagagg tcgtgaagaa gatgaagaac tactggcggc agctgctgaa cgccaagctg     5280

attacccaga gaaagttcga caatctgacc aaggccgaga gaggcggcct gagcgaactg     5340

gataaggccg gcttcatcaa gagacagctg gtggaaaccc ggcagatcac aaagcacgtg     5400

gcacagatcc tggactcccg gatgaacact aagtacgacg agaatgacaa gctgatccgg     5460

gaagtgaaag tgatcaccct gaagtccaag ctggtgtccg atttccggaa ggatttccag     5520

ttttacaaag tgcgcgagat caacaactac caccacgccc acgacgccta cctgaacgcc     5580

gtcgtgggaa ccgccctgat caaaaagtac cctaagctgg aaagcgagtt cgtgtacggc     5640

gactacaagg tgtacgacgt gcggaagatg atcgccaaga gcgagcagga aatcggcaag     5700

gctaccgcca agtacttctt ctacagcaac atcatgaact ttttcaagac cgagattacc     5760

ctggccaacg gcgagatccg gaagcggcct ctgatcgaga caaacggcga aaccggggag     5820

atcgtgtggg ataagggccg ggattttgcc accgtgcgga aagtgctgag catgccccaa     5880

gtgaatatcg tgaaaaagac cgaggtgcag acaggcggct tcagcaaaga gtctatcctg     5940

cccaagagga acagcgataa gctgatcgcc agaaagaagg actgggaccc taagaagtac     6000

ggcggcttcg acagccccac cgtggcctat tctgtgctgg tggtggccaa agtggaaaag     6060

ggcaagtcca agaaactgaa gagtgtgaaa gagctgctgg ggatcaccat catggaaaga     6120

agcagcttcg agaagaatcc catcgacttt ctggaagcca agggctacaa agaagtgaaa     6180

aaggacctga tcatcaagct gcctaagtac tccctgttcg agctggaaaa cggccggaag     6240

agaatgctgg cctctgccgg cgaactgcag aagggaaacg aactggccct gccctccaaa     6300

tatgtgaact tcctgtacct ggccagccac tatgagaagc tgaagggctc ccccgaggat     6360

aatgagcaga aacagctgtt tgtggaacag cacaagcact acctggacga gatcatcgag     6420

cagatcagcg agttctccaa gagagtgatc ctggccgacg ctaatctgga caaagtgctg     6480

tccgcctaca acaagcaccg ggataagccc atcagagagc aggccgagaa tatcatccac     6540

ctgtttaccc tgaccaatct gggagcccct gccgccttca agtactttga caccaccatc     6600

gaccggaaga ggtacaccag caccaaagag gtgctggacg ccaccctgat ccaccagagc     6660

atcaccggcc tgtacgagac acggatcgac ctgtctcagc tgggaggcga caagcgtcct     6720

gctgctacta agaaagctgg tcaagctaag aaaaagaaag ctagcggcag cggcgccacc     6780

aacttcagcc tgctgaagca ggccggcgac gtggaggaga accccggccc catggtgtct     6840

aagggcgaag agctgattaa ggagaacatg cacatgaagc tgtatatgga gggcaccgtg     6900

aacaaccacc acttcaagtg cacatccgag ggcgaaggca agccctacga gggcacccag     6960

accatgagaa tcaaggtggt cgagggcggc cctctcccct tcgccttcga catcctggct     7020

accagcttca tgtacggcag cagaaccttc atcaaccaca cccagggcat ccccgacttc     7080

tttaagcagt ccttccctga gggcttcaca tgggagagag tcaccacata cgaagacggg     7140

ggcgtgctga ccgctaccca ggacaccagc ctccaggacg gctgcctcat ctacaacgtc     7200

aagatcagag gggtgaactt cccatccaac ggccctgtga tgcagaagaa aacactcggc     7260

tgggaggcca acaccgagat gctgtacccc gctgacggcg gcctggaagg cagaagcgac     7320

atggccctga agctcgtggg cgggggccac ctgatctgca acttcaagac cacatacaga     7380

tccaagaaac ccgctaagaa cctcaagatg cccggcgtct actatgtgga ccacagactg     7440

gaaagaatca aggaggccga caaagagacc tacgtcgagc agcacgaggt ggctgtggcc     7500

agatactgcg acctccctag caaactgggg cacaaactta attgaacgcg ttaagtcgac     7560

aatcaacctc tggattacaa aatttgtgaa agattgactg gtattcttaa ctatgttgct     7620

ccttttacgc tatgtggata cgctgcttta atgcctttgt atcatgctat tgcttcccgt     7680

atggctttca ttttctcctc cttgtataaa tcctggttgc tgtctcttta tgaggagttg     7740

tggcccgttg tcaggcaacg tggcgtggtg tgcactgtgt ttgctgacgc aacccccact     7800

ggttggggca ttgccaccac ctgtcagctc ctttccggga ctttcgcttt ccccctccct     7860

attgccacgg cggaactcat cgccgcctgc cttgcccgct gctggacagg ggctcggctg     7920

ttgggcactg acaattccgt ggtgttgtcg gggaaatcat cgtcctttcc ttggctgctc     7980

gcctgtgttg ccacctggat tctgcgcggg acgtccttct gctacgtccc ttcggccctc     8040

aatccagcgg accttccttc ccgcggcctg ctgccggctc tgcggcctct tccgcgtctt     8100

cgccttcgcc ctcagacgag tcggatctcc ctttgggccg cctccccgcg tcgactttaa     8160

gaccaatgac ttacaaggca gctgtagatc ttagccactt tttaaaagaa aaggggggac     8220

tggaagggct aattcactcc caacgaagac aagatctgct ttttgcttgt actgggtctc     8280

tctggttaga ccagatctga gcctgggagc tctctggcta actagggaac ccactgctta     8340

agcctcaata aagcttgcct tgagtgcttc aagtagtgtg tgcccgtctg ttgtgtgact     8400

ctggtaacta gagatccctc agaccctttt agtcagtgtg gaaaatctct agcagtacgt     8460

atagtagttc atgtcatctt attattcagt atttataact tgcaaagaaa tgaatatcag     8520

agagtgagag gaacttgttt attgcagctt ataatggtta caaataaagc aatagcatca     8580

caaatttcac aaataaagca tttttttcac tgcattctag ttgtggtttg tccaaactca     8640

tcaatgtatc ttatcatgtc tggctctagc tatcccgccc ctaactccgc ccatcccgcc     8700

cctaactccg cccagttccg cccattctcc gccccatggc tgactaattt tttttattta     8760

tgcagaggcc gaggccgcct cggcctctga gctattccag aagtagtgag gaggcttttt     8820

tggaggccta gggacgtacc caattcgccc tatagtgagt cgtattacgc gcgctcactg     8880

gccgtcgttt tacaacgtcg tgactgggaa aaccctggcg ttacccaact taatcgcctt     8940

gcagcacatc cccctttcgc cagctggcgt aatagcgaag aggcccgcac cgatcgccct     9000

tcccaacagt tgcgcagcct gaatggcgaa tgggacgcgc cctgtagcgg cgcattaagc     9060

gcggcgggtg tggtggttac gcgcagcgtg accgctacac ttgccagcgc cctagcgccc     9120

gctcctttcg ctttcttccc ttcctttctc gccacgttcg ccggctttcc ccgtcaagct     9180

ctaaatcggg ggctcccttt agggttccga tttagtgctt tacggcacct cgaccccaaa     9240

aaacttgatt agggtgatgg ttcacgtagt gggccatcgc cctgatagac ggtttttcgc     9300

cctttgacgt tggagtccac gttctttaat agtggactct tgttccaaac tggaacaaca     9360

ctcaacccta tctcggtcta ttcttttgat ttataaggga ttttgccgat ttcggcctat     9420

tggttaaaaa atgagctgat ttaacaaaaa tttaacgcga attttaacaa aatattaacg     9480

cttacaattt aggtggcact tttcggggaa atgtgcgcgg aacccctatt tgtttatttt     9540

tctaaataca ttcaaatatg tatccgctca tgagacaata accctgataa atgcttcaat     9600

aatattgaaa aaggaagagt atgagtattc aacatttccg tgtcgccctt attccctttt     9660

ttgcggcatt ttgccttcct gtttttgctc acccagaaac gctggtgaaa gtaaaagatg     9720

ctgaagatca gttgggtgca cgagtgggtt acatcgaact ggatctcaac agcggtaaga     9780

tccttgagag ttttcgcccc gaagaacgtt ttccaatgat gagcactttt aaagttctgc     9840

tatgtggcgc ggtattatcc cgtattgacg ccgggcaaga gcaactcggt cgccgcatac     9900

actattctca gaatgacttg gttgagtact caccagtcac agaaaagcat cttacggatg     9960

gcatgacagt aagagaatta tgcagtgctg ccataaccat gagtgataac actgcggcca    10020

acttacttct gacaacgatc ggaggaccga aggagctaac cgcttttttg cacaacatgg    10080

gggatcatgt aactcgcctt gatcgttggg aaccggagct gaatgaagcc ataccaaacg    10140

acgagcgtga caccacgatg cctgtagcaa tggcaacaac gttgcgcaaa ctattaactg    10200

gcgaactact tactctagct tcccggcaac aattaataga ctggatggag gcggataaag    10260

ttgcaggacc acttctgcgc tcggcccttc cggctggctg gtttattgct gataaatctg    10320

gagccggtga gcgtgggtct cgcggtatca ttgcagcact ggggccagat ggtaagccct    10380

cccgtatcgt agttatctac acgacgggga gtcaggcaac tatggatgaa cgaaatagac    10440

agatcgctga gataggtgcc tcactgatta agcattggta actgtcagac caagtttact    10500

catatatact ttagattgat ttaaaacttc atttttaatt taaaaggatc taggtgaaga    10560

tcctttttga taatctcatg accaaaatcc cttaacgtga gttttcgttc cactgagcgt    10620

cagaccccgt agaaaagatc aaaggatctt cttgagatcc tttttttctg cgcgtaatct    10680

gctgcttgca aacaaaaaaa ccaccgctac cagcggtggt ttgtttgccg gatcaagagc    10740

taccaactct ttttccgaag gtaactggct tcagcagagc gcagatacca aatactgttc    10800

ttctagtgta gccgtagtta ggccaccact tcaagaactc tgtagcaccg cctacatacc    10860

tcgctctgct aatcctgtta ccagtggctg ctgccagtgg cgataagtcg tgtcttaccg    10920

ggttggactc aagacgatag ttaccggata aggcgcagcg gtcgggctga acggggggtt    10980

cgtgcacaca gcccagcttg gagcgaacga cctacaccga actgagatac ctacagcgtg    11040

agctatgaga aagcgccacg cttcccgaag ggagaaaggc ggacaggtat ccggtaagcg    11100

gcagggtcgg aacaggagag cgcacgaggg agcttccagg gggaaacgcc tggtatcttt    11160

atagtcctgt cgggtttcgc cacctctgac ttgagcgtcg atttttgtga tgctcgtcag    11220

gggggcggag cctatggaaa aacgccagca acgcggcctt tttacggttc ctggcctttt    11280

gctggccttt tgctcacatg ttctttcctg cgttatcccc tgattctgtg gataaccgta    11340

ttaccgcctt tgagtgagct gataccgctc gccgcagccg aacgaccgag cgcagcgagt    11400

cagtgagcga ggaagcggaa gagcgcccaa tacgcaaacc gcctctcccc gcgcgttggc    11460

cgattcatta atgcagctgg cacgacaggt ttcccgactg gaaagcgggc agtgagcgca    11520

acgcaattaa tgtgagttag ctcactcatt aggcacccca ggctttacac tttatgcttc    11580

cggctcgtat gttgtgtgga attgtgagcg gataacaatt tcacacagga aacagctatg    11640

accatgatta cgccaagcgc gcaattaacc ctcactaaag ggaacaaaag ctggagctgc    11700

aagc                                                                 11704


<210>  13
<211>  2351
<212>  PRT
<213>  Homo sapiens

<400>  13

Met Gln Ile Glu Leu Ser Thr Cys Phe Phe Leu Cys Leu Leu Arg Phe 
1               5                   10                  15      


Cys Phe Ser Ala Thr Arg Arg Tyr Tyr Leu Gly Ala Val Glu Leu Ser 
            20                  25                  30          


Trp Asp Tyr Met Gln Ser Asp Leu Gly Glu Leu Pro Val Asp Ala Arg 
        35                  40                  45              


Phe Pro Pro Arg Val Pro Lys Ser Phe Pro Phe Asn Thr Ser Val Val 
    50                  55                  60                  


Tyr Lys Lys Thr Leu Phe Val Glu Phe Thr Asp His Leu Phe Asn Ile 
65                  70                  75                  80  


Ala Lys Pro Arg Pro Pro Trp Met Gly Leu Leu Gly Pro Thr Ile Gln 
                85                  90                  95      


Ala Glu Val Tyr Asp Thr Val Val Ile Thr Leu Lys Asn Met Ala Ser 
            100                 105                 110         


His Pro Val Ser Leu His Ala Val Gly Val Ser Tyr Trp Lys Ala Ser 
        115                 120                 125             


Glu Gly Ala Glu Tyr Asp Asp Gln Thr Ser Gln Arg Glu Lys Glu Asp 
    130                 135                 140                 


Asp Lys Val Phe Pro Gly Gly Ser His Thr Tyr Val Trp Gln Val Leu 
145                 150                 155                 160 


Lys Glu Asn Gly Pro Met Ala Ser Asp Pro Leu Cys Leu Thr Tyr Ser 
                165                 170                 175     


Tyr Leu Ser His Val Asp Leu Val Lys Asp Leu Asn Ser Gly Leu Ile 
            180                 185                 190         


Gly Ala Leu Leu Val Cys Arg Glu Gly Ser Leu Ala Lys Glu Lys Thr 
        195                 200                 205             


Gln Thr Leu His Lys Phe Ile Leu Leu Phe Ala Val Phe Asp Glu Gly 
    210                 215                 220                 


Lys Ser Trp His Ser Glu Thr Lys Asn Ser Leu Met Gln Asp Arg Asp 
225                 230                 235                 240 


Ala Ala Ser Ala Arg Ala Trp Pro Lys Met His Thr Val Asn Gly Tyr 
                245                 250                 255     


Val Asn Arg Ser Leu Pro Gly Leu Ile Gly Cys His Arg Lys Ser Val 
            260                 265                 270         


Tyr Trp His Val Ile Gly Met Gly Thr Thr Pro Glu Val His Ser Ile 
        275                 280                 285             


Phe Leu Glu Gly His Thr Phe Leu Val Arg Asn His Arg Gln Ala Ser 
    290                 295                 300                 


Leu Glu Ile Ser Pro Ile Thr Phe Leu Thr Ala Gln Thr Leu Leu Met 
305                 310                 315                 320 


Asp Leu Gly Gln Phe Leu Leu Phe Cys His Ile Ser Ser His Gln His 
                325                 330                 335     


Asp Gly Met Glu Ala Tyr Val Lys Val Asp Ser Cys Pro Glu Glu Pro 
            340                 345                 350         


Gln Leu Arg Met Lys Asn Asn Glu Glu Ala Glu Asp Tyr Asp Asp Asp 
        355                 360                 365             


Leu Thr Asp Ser Glu Met Asp Val Val Arg Phe Asp Asp Asp Asn Ser 
    370                 375                 380                 


Pro Ser Phe Ile Gln Ile Arg Ser Val Ala Lys Lys His Pro Lys Thr 
385                 390                 395                 400 


Trp Val His Tyr Ile Ala Ala Glu Glu Glu Asp Trp Asp Tyr Ala Pro 
                405                 410                 415     


Leu Val Leu Ala Pro Asp Asp Arg Ser Tyr Lys Ser Gln Tyr Leu Asn 
            420                 425                 430         


Asn Gly Pro Gln Arg Ile Gly Arg Lys Tyr Lys Lys Val Arg Phe Met 
        435                 440                 445             


Ala Tyr Thr Asp Glu Thr Phe Lys Thr Arg Glu Ala Ile Gln His Glu 
    450                 455                 460                 


Ser Gly Ile Leu Gly Pro Leu Leu Tyr Gly Glu Val Gly Asp Thr Leu 
465                 470                 475                 480 


Leu Ile Ile Phe Lys Asn Gln Ala Ser Arg Pro Tyr Asn Ile Tyr Pro 
                485                 490                 495     


His Gly Ile Thr Asp Val Arg Pro Leu Tyr Ser Arg Arg Leu Pro Lys 
            500                 505                 510         


Gly Val Lys His Leu Lys Asp Phe Pro Ile Leu Pro Gly Glu Ile Phe 
        515                 520                 525             


Lys Tyr Lys Trp Thr Val Thr Val Glu Asp Gly Pro Thr Lys Ser Asp 
    530                 535                 540                 


Pro Arg Cys Leu Thr Arg Tyr Tyr Ser Ser Phe Val Asn Met Glu Arg 
545                 550                 555                 560 


Asp Leu Ala Ser Gly Leu Ile Gly Pro Leu Leu Ile Cys Tyr Lys Glu 
                565                 570                 575     


Ser Val Asp Gln Arg Gly Asn Gln Ile Met Ser Asp Lys Arg Asn Val 
            580                 585                 590         


Ile Leu Phe Ser Val Phe Asp Glu Asn Arg Ser Trp Tyr Leu Thr Glu 
        595                 600                 605             


Asn Ile Gln Arg Phe Leu Pro Asn Pro Ala Gly Val Gln Leu Glu Asp 
    610                 615                 620                 


Pro Glu Phe Gln Ala Ser Asn Ile Met His Ser Ile Asn Gly Tyr Val 
625                 630                 635                 640 


Phe Asp Ser Leu Gln Leu Ser Val Cys Leu His Glu Val Ala Tyr Trp 
                645                 650                 655     


Tyr Ile Leu Ser Ile Gly Ala Gln Thr Asp Phe Leu Ser Val Phe Phe 
            660                 665                 670         


Ser Gly Tyr Thr Phe Lys His Lys Met Val Tyr Glu Asp Thr Leu Thr 
        675                 680                 685             


Leu Phe Pro Phe Ser Gly Glu Thr Val Phe Met Ser Met Glu Asn Pro 
    690                 695                 700                 


Gly Leu Trp Ile Leu Gly Cys His Asn Ser Asp Phe Arg Asn Arg Gly 
705                 710                 715                 720 


Met Thr Ala Leu Leu Lys Val Ser Ser Cys Asp Lys Asn Thr Gly Asp 
                725                 730                 735     


Tyr Tyr Glu Asp Ser Tyr Glu Asp Ile Ser Ala Tyr Leu Leu Ser Lys 
            740                 745                 750         


Asn Asn Ala Ile Glu Pro Arg Ser Phe Ser Gln Asn Ser Arg His Pro 
        755                 760                 765             


Ser Thr Arg Gln Lys Gln Phe Asn Ala Thr Thr Ile Pro Glu Asn Asp 
    770                 775                 780                 


Ile Glu Lys Thr Asp Pro Trp Phe Ala His Arg Thr Pro Met Pro Lys 
785                 790                 795                 800 


Ile Gln Asn Val Ser Ser Ser Asp Leu Leu Met Leu Leu Arg Gln Ser 
                805                 810                 815     


Pro Thr Pro His Gly Leu Ser Leu Ser Asp Leu Gln Glu Ala Lys Tyr 
            820                 825                 830         


Glu Thr Phe Ser Asp Asp Pro Ser Pro Gly Ala Ile Asp Ser Asn Asn 
        835                 840                 845             


Ser Leu Ser Glu Met Thr His Phe Arg Pro Gln Leu His His Ser Gly 
    850                 855                 860                 


Asp Met Val Phe Thr Pro Glu Ser Gly Leu Gln Leu Arg Leu Asn Glu 
865                 870                 875                 880 


Lys Leu Gly Thr Thr Ala Ala Thr Glu Leu Lys Lys Leu Asp Phe Lys 
                885                 890                 895     


Val Ser Ser Thr Ser Asn Asn Leu Ile Ser Thr Ile Pro Ser Asp Asn 
            900                 905                 910         


Leu Ala Ala Gly Thr Asp Asn Thr Ser Ser Leu Gly Pro Pro Ser Met 
        915                 920                 925             


Pro Val His Tyr Asp Ser Gln Leu Asp Thr Thr Leu Phe Gly Lys Lys 
    930                 935                 940                 


Ser Ser Pro Leu Thr Glu Ser Gly Gly Pro Leu Ser Leu Ser Glu Glu 
945                 950                 955                 960 


Asn Asn Asp Ser Lys Leu Leu Glu Ser Gly Leu Met Asn Ser Gln Glu 
                965                 970                 975     


Ser Ser Trp Gly Lys Asn Val Ser Ser Thr Glu Ser Gly Arg Leu Phe 
            980                 985                 990         


Lys Gly Lys Arg Ala His Gly Pro  Ala Leu Leu Thr Lys  Asp Asn Ala 
        995                 1000                 1005             


Leu Phe  Lys Val Ser Ile Ser  Leu Leu Lys Thr Asn  Lys Thr Ser 
    1010                 1015                 1020             


Asn Asn  Ser Ala Thr Asn Arg  Lys Thr His Ile Asp  Gly Pro Ser 
    1025                 1030                 1035             


Leu Leu  Ile Glu Asn Ser Pro  Ser Val Trp Gln Asn  Ile Leu Glu 
    1040                 1045                 1050             


Ser Asp  Thr Glu Phe Lys Lys  Val Thr Pro Leu Ile  His Asp Arg 
    1055                 1060                 1065             


Met Leu  Met Asp Lys Asn Ala  Thr Ala Leu Arg Leu  Asn His Met 
    1070                 1075                 1080             


Ser Asn  Lys Thr Thr Ser Ser  Lys Asn Met Glu Met  Val Gln Gln 
    1085                 1090                 1095             


Lys Lys  Glu Gly Pro Ile Pro  Pro Asp Ala Gln Asn  Pro Asp Met 
    1100                 1105                 1110             


Ser Phe  Phe Lys Met Leu Phe  Leu Pro Glu Ser Ala  Arg Trp Ile 
    1115                 1120                 1125             


Gln Arg  Thr His Gly Lys Asn  Ser Leu Asn Ser Gly  Gln Gly Pro 
    1130                 1135                 1140             


Ser Pro  Lys Gln Leu Val Ser  Leu Gly Pro Glu Lys  Ser Val Glu 
    1145                 1150                 1155             


Gly Gln  Asn Phe Leu Ser Glu  Lys Asn Lys Val Val  Val Gly Lys 
    1160                 1165                 1170             


Gly Glu  Phe Thr Lys Asp Val  Gly Leu Lys Glu Met  Val Phe Pro 
    1175                 1180                 1185             


Ser Ser  Arg Asn Leu Phe Leu  Thr Asn Leu Asp Asn  Leu His Glu 
    1190                 1195                 1200             


Asn Asn  Thr His Asn Gln Glu  Lys Lys Ile Gln Glu  Glu Ile Glu 
    1205                 1210                 1215             


Lys Lys  Glu Thr Leu Ile Gln  Glu Asn Val Val Leu  Pro Gln Ile 
    1220                 1225                 1230             


His Thr  Val Thr Gly Thr Lys  Asn Phe Met Lys Asn  Leu Phe Leu 
    1235                 1240                 1245             


Leu Ser  Thr Arg Gln Asn Val  Glu Gly Ser Tyr Asp  Gly Ala Tyr 
    1250                 1255                 1260             


Ala Pro  Val Leu Gln Asp Phe  Arg Ser Leu Asn Asp  Ser Thr Asn 
    1265                 1270                 1275             


Arg Thr  Lys Lys His Thr Ala  His Phe Ser Lys Lys  Gly Glu Glu 
    1280                 1285                 1290             


Glu Asn  Leu Glu Gly Leu Gly  Asn Gln Thr Lys Gln  Ile Val Glu 
    1295                 1300                 1305             


Lys Tyr  Ala Cys Thr Thr Arg  Ile Ser Pro Asn Thr  Ser Gln Gln 
    1310                 1315                 1320             


Asn Phe  Val Thr Gln Arg Ser  Lys Arg Ala Leu Lys  Gln Phe Arg 
    1325                 1330                 1335             


Leu Pro  Leu Glu Glu Thr Glu  Leu Glu Lys Arg Ile  Ile Val Asp 
    1340                 1345                 1350             


Asp Thr  Ser Thr Gln Trp Ser  Lys Asn Met Lys His  Leu Thr Pro 
    1355                 1360                 1365             


Ser Thr  Leu Thr Gln Ile Asp  Tyr Asn Glu Lys Glu  Lys Gly Ala 
    1370                 1375                 1380             


Ile Thr  Gln Ser Pro Leu Ser  Asp Cys Leu Thr Arg  Ser His Ser 
    1385                 1390                 1395             


Ile Pro  Gln Ala Asn Arg Ser  Pro Leu Pro Ile Ala  Lys Val Ser 
    1400                 1405                 1410             


Ser Phe  Pro Ser Ile Arg Pro  Ile Tyr Leu Thr Arg  Val Leu Phe 
    1415                 1420                 1425             


Gln Asp  Asn Ser Ser His Leu  Pro Ala Ala Ser Tyr  Arg Lys Lys 
    1430                 1435                 1440             


Asp Ser  Gly Val Gln Glu Ser  Ser His Phe Leu Gln  Gly Ala Lys 
    1445                 1450                 1455             


Lys Asn  Asn Leu Ser Leu Ala  Ile Leu Thr Leu Glu  Met Thr Gly 
    1460                 1465                 1470             


Asp Gln  Arg Glu Val Gly Ser  Leu Gly Thr Ser Ala  Thr Asn Ser 
    1475                 1480                 1485             


Val Thr  Tyr Lys Lys Val Glu  Asn Thr Val Leu Pro  Lys Pro Asp 
    1490                 1495                 1500             


Leu Pro  Lys Thr Ser Gly Lys  Val Glu Leu Leu Pro  Lys Val His 
    1505                 1510                 1515             


Ile Tyr  Gln Lys Asp Leu Phe  Pro Thr Glu Thr Ser  Asn Gly Ser 
    1520                 1525                 1530             


Pro Gly  His Leu Asp Leu Val  Glu Gly Ser Leu Leu  Gln Gly Thr 
    1535                 1540                 1545             


Glu Gly  Ala Ile Lys Trp Asn  Glu Ala Asn Arg Pro  Gly Lys Val 
    1550                 1555                 1560             


Pro Phe  Leu Arg Val Ala Thr  Glu Ser Ser Ala Lys  Thr Pro Ser 
    1565                 1570                 1575             


Lys Leu  Leu Asp Pro Leu Ala  Trp Asp Asn His Tyr  Gly Thr Gln 
    1580                 1585                 1590             


Ile Pro  Lys Glu Glu Trp Lys  Ser Gln Glu Lys Ser  Pro Glu Lys 
    1595                 1600                 1605             


Thr Ala  Phe Lys Lys Lys Asp  Thr Ile Leu Ser Leu  Asn Ala Cys 
    1610                 1615                 1620             


Glu Ser  Asn His Ala Ile Ala  Ala Ile Asn Glu Gly  Gln Asn Lys 
    1625                 1630                 1635             


Pro Glu  Ile Glu Val Thr Trp  Ala Lys Gln Gly Arg  Thr Glu Arg 
    1640                 1645                 1650             


Leu Cys  Ser Gln Asn Pro Pro  Val Leu Lys Arg His  Gln Arg Glu 
    1655                 1660                 1665             


Ile Thr  Arg Thr Thr Leu Gln  Ser Asp Gln Glu Glu  Ile Asp Tyr 
    1670                 1675                 1680             


Asp Asp  Thr Ile Ser Val Glu  Met Lys Lys Glu Asp  Phe Asp Ile 
    1685                 1690                 1695             


Tyr Asp  Glu Asp Glu Asn Gln  Ser Pro Arg Ser Phe  Gln Lys Lys 
    1700                 1705                 1710             


Thr Arg  His Tyr Phe Ile Ala  Ala Val Glu Arg Leu  Trp Asp Tyr 
    1715                 1720                 1725             


Gly Met  Ser Ser Ser Pro His  Val Leu Arg Asn Arg  Ala Gln Ser 
    1730                 1735                 1740             


Gly Ser  Val Pro Gln Phe Lys  Lys Val Val Phe Gln  Glu Phe Thr 
    1745                 1750                 1755             


Asp Gly  Ser Phe Thr Gln Pro  Leu Tyr Arg Gly Glu  Leu Asn Glu 
    1760                 1765                 1770             


His Leu  Gly Leu Leu Gly Pro  Tyr Ile Arg Ala Glu  Val Glu Asp 
    1775                 1780                 1785             


Asn Ile  Met Val Thr Phe Arg  Asn Gln Ala Ser Arg  Pro Tyr Ser 
    1790                 1795                 1800             


Phe Tyr  Ser Ser Leu Ile Ser  Tyr Glu Glu Asp Gln  Arg Gln Gly 
    1805                 1810                 1815             


Ala Glu  Pro Arg Lys Asn Phe  Val Lys Pro Asn Glu  Thr Lys Thr 
    1820                 1825                 1830             


Tyr Phe  Trp Lys Val Gln His  His Met Ala Pro Thr  Lys Asp Glu 
    1835                 1840                 1845             


Phe Asp  Cys Lys Ala Trp Ala  Tyr Phe Ser Asp Val  Asp Leu Glu 
    1850                 1855                 1860             


Lys Asp  Val His Ser Gly Leu  Ile Gly Pro Leu Leu  Val Cys His 
    1865                 1870                 1875             


Thr Asn  Thr Leu Asn Pro Ala  His Gly Arg Gln Val  Thr Val Gln 
    1880                 1885                 1890             


Glu Phe  Ala Leu Phe Phe Thr  Ile Phe Asp Glu Thr  Lys Ser Trp 
    1895                 1900                 1905             


Tyr Phe  Thr Glu Asn Met Glu  Arg Asn Cys Arg Ala  Pro Ser Asn 
    1910                 1915                 1920             


Ile Gln  Met Glu Asp Pro Thr  Phe Lys Glu Asn Tyr  Arg Phe His 
    1925                 1930                 1935             


Ala Ile  Asn Gly Tyr Ile Met  Asp Thr Leu Pro Gly  Leu Val Met 
    1940                 1945                 1950             


Ala Gln  Asp Gln Arg Ile Arg  Trp Tyr Leu Leu Ser  Met Gly Ser 
    1955                 1960                 1965             


Asn Glu  Asn Ile His Ser Ile  His Phe Ser Gly His  Val Phe Thr 
    1970                 1975                 1980             


Val Arg  Lys Lys Glu Glu Tyr  Lys Met Ala Leu Tyr  Asn Leu Tyr 
    1985                 1990                 1995             


Pro Gly  Val Phe Glu Thr Val  Glu Met Leu Pro Ser  Lys Ala Gly 
    2000                 2005                 2010             


Ile Trp  Arg Val Glu Cys Leu  Ile Gly Glu His Leu  His Ala Gly 
    2015                 2020                 2025             


Met Ser  Thr Leu Phe Leu Val  Tyr Ser Asn Lys Cys  Gln Thr Pro 
    2030                 2035                 2040             


Leu Gly  Met Ala Ser Gly His  Ile Arg Asp Phe Gln  Ile Thr Ala 
    2045                 2050                 2055             


Ser Gly  Gln Tyr Gly Gln Trp  Ala Pro Lys Leu Ala  Arg Leu His 
    2060                 2065                 2070             


Tyr Ser  Gly Ser Ile Asn Ala  Trp Ser Thr Lys Glu  Pro Phe Ser 
    2075                 2080                 2085             


Trp Ile  Lys Val Asp Leu Leu  Ala Pro Met Ile Ile  His Gly Ile 
    2090                 2095                 2100             


Lys Thr  Gln Gly Ala Arg Gln  Lys Phe Ser Ser Leu  Tyr Ile Ser 
    2105                 2110                 2115             


Gln Phe  Ile Ile Met Tyr Ser  Leu Asp Gly Lys Lys  Trp Gln Thr 
    2120                 2125                 2130             


Tyr Arg  Gly Asn Ser Thr Gly  Thr Leu Met Val Phe  Phe Gly Asn 
    2135                 2140                 2145             


Val Asp  Ser Ser Gly Ile Lys  His Asn Ile Phe Asn  Pro Pro Ile 
    2150                 2155                 2160             


Ile Ala  Arg Tyr Ile Arg Leu  His Pro Thr His Tyr  Ser Ile Arg 
    2165                 2170                 2175             


Ser Thr  Leu Arg Met Glu Leu  Met Gly Cys Asp Leu  Asn Ser Cys 
    2180                 2185                 2190             


Ser Met  Pro Leu Gly Met Glu  Ser Lys Ala Ile Ser  Asp Ala Gln 
    2195                 2200                 2205             


Ile Thr  Ala Ser Ser Tyr Phe  Thr Asn Met Phe Ala  Thr Trp Ser 
    2210                 2215                 2220             


Pro Ser  Lys Ala Arg Leu His  Leu Gln Gly Arg Ser  Asn Ala Trp 
    2225                 2230                 2235             


Arg Pro  Gln Val Asn Asn Pro  Lys Glu Trp Leu Gln  Val Asp Phe 
    2240                 2245                 2250             


Gln Lys  Thr Met Lys Val Thr  Gly Val Thr Thr Gln  Gly Val Lys 
    2255                 2260                 2265             


Ser Leu  Leu Thr Ser Met Tyr  Val Lys Glu Phe Leu  Ile Ser Ser 
    2270                 2275                 2280             


Ser Gln  Asp Gly His Gln Trp  Thr Leu Phe Phe Gln  Asn Gly Lys 
    2285                 2290                 2295             


Val Lys  Val Phe Gln Gly Asn  Gln Asp Ser Phe Thr  Pro Val Val 
    2300                 2305                 2310             


Asn Ser  Leu Asp Pro Pro Leu  Leu Thr Arg Tyr Leu  Arg Ile His 
    2315                 2320                 2325             


Pro Gln  Ser Trp Val His Gln  Ile Ala Leu Arg Met  Glu Val Leu 
    2330                 2335                 2340             


Gly Cys  Glu Ala Gln Asp Leu  Tyr 
    2345                 2350     


<210>  14
<211>  2319
<212>  PRT
<213>  Mus musculus

<400>  14

Met Gln Ile Ala Leu Phe Ala Cys Phe Phe Leu Ser Leu Phe Asn Phe 
1               5                   10                  15      


Cys Ser Ser Ala Ile Arg Arg Tyr Tyr Leu Gly Ala Val Glu Leu Ser 
            20                  25                  30          


Trp Asn Tyr Ile Gln Ser Asp Leu Leu Ser Val Leu His Thr Asp Ser 
        35                  40                  45              


Arg Phe Leu Pro Arg Met Ser Thr Ser Phe Pro Phe Asn Thr Ser Ile 
    50                  55                  60                  


Met Tyr Lys Lys Thr Val Phe Val Glu Tyr Lys Asp Gln Leu Phe Asn 
65                  70                  75                  80  


Ile Ala Lys Pro Arg Pro Pro Trp Met Gly Leu Leu Gly Pro Thr Ile 
                85                  90                  95      


Trp Thr Glu Val His Asp Thr Val Val Ile Thr Leu Lys Asn Met Ala 
            100                 105                 110         


Ser His Pro Val Ser Leu His Ala Val Gly Val Ser Tyr Trp Lys Ala 
        115                 120                 125             


Ser Glu Gly Asp Glu Tyr Glu Asp Gln Thr Ser Gln Met Glu Lys Glu 
    130                 135                 140                 


Asp Asp Lys Val Phe Pro Gly Glu Ser His Thr Tyr Val Trp Gln Val 
145                 150                 155                 160 


Leu Lys Glu Asn Gly Pro Met Ala Ser Asp Pro Pro Cys Leu Thr Tyr 
                165                 170                 175     


Ser Tyr Met Ser His Val Asp Leu Val Lys Asp Leu Asn Ser Gly Leu 
            180                 185                 190         


Ile Gly Ala Leu Leu Val Cys Lys Glu Gly Ser Leu Ser Lys Glu Arg 
        195                 200                 205             


Thr Gln Met Leu Tyr Gln Phe Val Leu Leu Phe Ala Val Phe Asp Glu 
    210                 215                 220                 


Gly Lys Ser Trp His Ser Glu Thr Asn Asp Ser Tyr Thr Gln Ser Met 
225                 230                 235                 240 


Asp Ser Ala Ser Ala Arg Asp Trp Pro Lys Met His Thr Val Asn Gly 
                245                 250                 255     


Tyr Val Asn Arg Ser Leu Pro Gly Leu Ile Gly Cys His Arg Lys Ser 
            260                 265                 270         


Val Tyr Trp His Val Ile Gly Met Gly Thr Thr Pro Glu Ile His Ser 
        275                 280                 285             


Ile Phe Leu Glu Gly His Thr Phe Phe Val Arg Asn His Arg Gln Ala 
    290                 295                 300                 


Ser Leu Glu Ile Ser Pro Ile Thr Phe Leu Thr Ala Gln Thr Leu Leu 
305                 310                 315                 320 


Ile Asp Leu Gly Gln Phe Leu Leu Phe Cys His Ile Ser Ser His Lys 
                325                 330                 335     


His Asp Gly Met Glu Ala Tyr Val Lys Val Asp Ser Cys Pro Glu Glu 
            340                 345                 350         


Ser Gln Trp Gln Lys Lys Asn Asn Asn Glu Glu Met Glu Asp Tyr Asp 
        355                 360                 365             


Asp Asp Leu Tyr Ser Glu Met Asp Met Phe Thr Leu Asp Tyr Asp Ser 
    370                 375                 380                 


Ser Pro Phe Ile Gln Ile Arg Ser Val Ala Lys Lys Tyr Pro Lys Thr 
385                 390                 395                 400 


Trp Ile His Tyr Ile Ser Ala Glu Glu Glu Asp Trp Asp Tyr Ala Pro 
                405                 410                 415     


Ser Val Pro Thr Ser Asp Asn Gly Ser Tyr Lys Ser Gln Tyr Leu Ser 
            420                 425                 430         


Asn Gly Pro His Arg Ile Gly Arg Lys Tyr Lys Lys Val Arg Phe Ile 
        435                 440                 445             


Ala Tyr Thr Asp Glu Thr Phe Lys Thr Arg Glu Thr Ile Gln His Glu 
    450                 455                 460                 


Ser Gly Leu Leu Gly Pro Leu Leu Tyr Gly Glu Val Gly Asp Thr Leu 
465                 470                 475                 480 


Leu Ile Ile Phe Lys Asn Gln Ala Ser Arg Pro Tyr Asn Ile Tyr Pro 
                485                 490                 495     


His Gly Ile Thr Asp Val Ser Pro Leu His Ala Arg Arg Leu Pro Arg 
            500                 505                 510         


Gly Ile Lys His Val Lys Asp Leu Pro Ile His Pro Gly Glu Ile Phe 
        515                 520                 525             


Lys Tyr Lys Trp Thr Val Thr Val Glu Asp Gly Pro Thr Lys Ser Asp 
    530                 535                 540                 


Pro Arg Cys Leu Thr Arg Tyr Tyr Ser Ser Phe Ile Asn Pro Glu Arg 
545                 550                 555                 560 


Asp Leu Ala Ser Gly Leu Ile Gly Pro Leu Leu Ile Cys Tyr Lys Glu 
                565                 570                 575     


Ser Val Asp Gln Arg Gly Asn Gln Met Met Ser Asp Lys Arg Asn Val 
            580                 585                 590         


Ile Leu Phe Ser Ile Phe Asp Glu Asn Gln Ser Trp Tyr Ile Thr Glu 
        595                 600                 605             


Asn Met Gln Arg Phe Leu Pro Asn Ala Ala Lys Thr Gln Pro Gln Asp 
    610                 615                 620                 


Pro Gly Phe Gln Ala Ser Asn Ile Met His Ser Ile Asn Gly Tyr Val 
625                 630                 635                 640 


Phe Asp Ser Leu Glu Leu Thr Val Cys Leu His Glu Val Ala Tyr Trp 
                645                 650                 655     


His Ile Leu Ser Val Gly Ala Gln Thr Asp Phe Leu Ser Ile Phe Phe 
            660                 665                 670         


Ser Gly Tyr Thr Phe Lys His Lys Met Val Tyr Glu Asp Thr Leu Thr 
        675                 680                 685             


Leu Phe Pro Phe Ser Gly Glu Thr Val Phe Met Ser Met Glu Asn Pro 
    690                 695                 700                 


Gly Leu Trp Val Leu Gly Cys His Asn Ser Asp Phe Arg Lys Arg Gly 
705                 710                 715                 720 


Met Thr Ala Leu Leu Lys Val Ser Ser Cys Asp Lys Ser Thr Ser Asp 
                725                 730                 735     


Tyr Tyr Glu Glu Ile Tyr Glu Asp Ile Pro Thr Gln Leu Val Asn Glu 
            740                 745                 750         


Asn Asn Val Ile Asp Pro Arg Ser Phe Phe Gln Asn Thr Asn His Pro 
        755                 760                 765             


Asn Thr Arg Lys Lys Lys Phe Lys Asp Ser Thr Ile Pro Lys Asn Asp 
    770                 775                 780                 


Met Glu Lys Ile Glu Pro Gln Phe Glu Glu Ile Ala Glu Met Leu Lys 
785                 790                 795                 800 


Val Gln Ser Val Ser Val Ser Asp Met Leu Met Leu Leu Gly Gln Ser 
                805                 810                 815     


His Pro Thr Pro His Gly Leu Phe Leu Ser Asp Gly Gln Glu Ala Ile 
            820                 825                 830         


Tyr Glu Ala Ile His Asp Asp His Ser Pro Asn Ala Ile Asp Ser Asn 
        835                 840                 845             


Glu Gly Pro Ser Lys Val Thr Gln Leu Arg Pro Glu Ser His His Ser 
    850                 855                 860                 


Glu Lys Ile Val Phe Thr Pro Gln Pro Gly Leu Gln Leu Arg Ser Asn 
865                 870                 875                 880 


Lys Ser Leu Glu Thr Thr Ile Glu Val Lys Trp Lys Lys Leu Gly Leu 
                885                 890                 895     


Gln Val Ser Ser Leu Pro Ser Asn Leu Met Thr Thr Thr Ile Leu Ser 
            900                 905                 910         


Asp Asn Leu Lys Ala Thr Phe Glu Lys Thr Asp Ser Ser Gly Phe Pro 
        915                 920                 925             


Asp Met Pro Val His Ser Ser Ser Lys Leu Ser Thr Thr Ala Phe Gly 
    930                 935                 940                 


Lys Lys Ala Tyr Ser Leu Val Gly Ser His Val Pro Leu Asn Val Ser 
945                 950                 955                 960 


Glu Glu Asn Ser Asp Ser Asn Ile Leu Asp Ser Thr Leu Met Tyr Ser 
                965                 970                 975     


Gln Glu Ser Leu Pro Arg Asp Asn Ile Leu Ser Met Glu Asn Asp Arg 
            980                 985                 990         


Leu Leu Arg Glu Lys Arg Phe His  Gly Ile Ala Leu Leu  Thr Lys Asp 
        995                 1000                 1005             


Asn Thr  Leu Phe Lys Asp Asn  Val Ser Leu Met Lys  Thr Asn Lys 
    1010                 1015                 1020             


Thr Tyr  Asn His Ser Thr Thr  Asn Glu Lys Leu His  Thr Glu Ser 
    1025                 1030                 1035             


Pro Thr  Ser Ile Glu Asn Ser  Thr Thr Asp Leu Gln  Asp Ala Ile 
    1040                 1045                 1050             


Leu Lys  Val Asn Ser Glu Ile  Gln Glu Val Thr Ala  Leu Ile His 
    1055                 1060                 1065             


Asp Gly  Thr Leu Leu Gly Lys  Asn Ser Thr Tyr Leu  Arg Leu Asn 
    1070                 1075                 1080             


His Met  Leu Asn Arg Thr Thr  Ser Thr Lys Asn Lys  Asp Ile Phe 
    1085                 1090                 1095             


His Arg  Lys Asp Glu Asp Pro  Ile Pro Gln Asp Glu  Glu Asn Thr 
    1100                 1105                 1110             


Ile Met  Pro Phe Ser Lys Met  Leu Phe Leu Ser Glu  Ser Ser Asn 
    1115                 1120                 1125             


Trp Phe  Lys Lys Thr Asn Gly  Asn Asn Ser Leu Asn  Ser Glu Gln 
    1130                 1135                 1140             


Glu His  Ser Pro Lys Gln Leu  Val Tyr Leu Met Phe  Lys Lys Tyr 
    1145                 1150                 1155             


Val Lys  Asn Gln Ser Phe Leu  Ser Glu Lys Asn Lys  Val Thr Val 
    1160                 1165                 1170             


Glu Gln  Asp Gly Phe Thr Lys  Asn Ile Gly Leu Lys  Asp Met Ala 
    1175                 1180                 1185             


Phe Pro  His Asn Met Ser Ile  Phe Leu Thr Thr Leu  Ser Asn Val 
    1190                 1195                 1200             


His Glu  Asn Gly Arg His Asn  Gln Glu Lys Asn Ile  Gln Glu Glu 
    1205                 1210                 1215             


Ile Glu  Lys Glu Ala Leu Ile  Glu Glu Lys Val Val  Leu Pro Gln 
    1220                 1225                 1230             


Val His  Glu Ala Thr Gly Ser  Lys Asn Phe Leu Lys  Asp Ile Leu 
    1235                 1240                 1245             


Ile Leu  Gly Thr Arg Gln Asn  Ile Ser Leu Tyr Glu  Val His Val 
    1250                 1255                 1260             


Pro Val  Leu Gln Asn Ile Thr  Ser Ile Asn Asn Ser  Thr Asn Thr 
    1265                 1270                 1275             


Val Gln  Ile His Met Glu His  Phe Phe Lys Arg Arg  Lys Asp Lys 
    1280                 1285                 1290             


Glu Thr  Asn Ser Glu Gly Leu  Val Asn Lys Thr Arg  Glu Met Val 
    1295                 1300                 1305             


Lys Asn  Tyr Pro Ser Gln Lys  Asn Ile Thr Thr Gln  Arg Ser Lys 
    1310                 1315                 1320             


Arg Ala  Leu Gly Gln Phe Arg  Leu Ser Thr Gln Trp  Leu Lys Thr 
    1325                 1330                 1335             


Ile Asn  Cys Ser Thr Gln Cys  Ile Ile Lys Gln Ile  Asp His Ser 
    1340                 1345                 1350             


Lys Glu  Met Lys Lys Phe Ile  Thr Lys Ser Ser Leu  Ser Asp Ser 
    1355                 1360                 1365             


Ser Val  Ile Lys Ser Thr Thr  Gln Thr Asn Ser Ser  Asp Ser His 
    1370                 1375                 1380             


Ile Val  Lys Thr Ser Ala Phe  Pro Pro Ile Asp Leu  Lys Arg Ser 
    1385                 1390                 1395             


Pro Phe  Gln Asn Lys Phe Ser  His Val Gln Ala Ser  Ser Tyr Ile 
    1400                 1405                 1410             


Tyr Asp  Phe Lys Thr Lys Ser  Ser Arg Ile Gln Glu  Ser Asn Asn 
    1415                 1420                 1425             


Phe Leu  Lys Glu Thr Lys Ile  Asn Asn Pro Ser Leu  Ala Ile Leu 
    1430                 1435                 1440             


Pro Trp  Asn Met Phe Ile Asp  Gln Gly Lys Phe Thr  Ser Pro Gly 
    1445                 1450                 1455             


Lys Ser  Asn Thr Asn Ser Val  Thr Tyr Lys Lys Arg  Glu Asn Ile 
    1460                 1465                 1470             


Ile Phe  Leu Lys Pro Thr Leu  Pro Glu Glu Ser Gly  Lys Ile Glu 
    1475                 1480                 1485             


Leu Leu  Pro Gln Val Ser Ile  Gln Glu Glu Glu Ile  Leu Pro Thr 
    1490                 1495                 1500             


Glu Thr  Ser His Gly Ser Pro  Gly His Leu Asn Leu  Met Lys Glu 
    1505                 1510                 1515             


Val Phe  Leu Gln Lys Ile Gln  Gly Pro Thr Lys Trp  Asn Lys Ala 
    1520                 1525                 1530             


Lys Arg  His Gly Glu Ser Ile  Lys Gly Lys Thr Glu  Ser Ser Lys 
    1535                 1540                 1545             


Asn Thr  Arg Ser Lys Leu Leu  Asn His His Ala Trp  Asp Tyr His 
    1550                 1555                 1560             


Tyr Ala  Ala Gln Ile Pro Lys  Asp Met Trp Lys Ser  Lys Glu Lys 
    1565                 1570                 1575             


Ser Pro  Glu Ile Ile Ser Ile  Lys Gln Glu Asp Thr  Ile Leu Ser 
    1580                 1585                 1590             


Leu Arg  Pro His Gly Asn Ser  His Ser Ile Gly Ala  Asn Glu Lys 
    1595                 1600                 1605             


Gln Asn  Trp Pro Gln Arg Glu  Thr Thr Trp Val Lys  Gln Gly Gln 
    1610                 1615                 1620             


Thr Gln  Arg Thr Cys Ser Gln  Ile Pro Pro Val Leu  Lys Arg His 
    1625                 1630                 1635             


Gln Arg  Glu Leu Ser Ala Phe  Gln Ser Glu Gln Glu  Ala Thr Asp 
    1640                 1645                 1650             


Tyr Asp  Asp Ala Ile Thr Ile  Glu Thr Ile Glu Asp  Phe Asp Ile 
    1655                 1660                 1665             


Tyr Ser  Glu Asp Ile Lys Gln  Gly Pro Arg Ser Phe  Gln Gln Lys 
    1670                 1675                 1680             


Thr Arg  His Tyr Phe Ile Ala  Ala Val Glu Arg Leu  Trp Asp Tyr 
    1685                 1690                 1695             


Gly Met  Ser Thr Ser His Val  Leu Arg Asn Arg Tyr  Gln Ser Asp 
    1700                 1705                 1710             


Asn Val  Pro Gln Phe Lys Lys  Val Val Phe Gln Glu  Phe Thr Asp 
    1715                 1720                 1725             


Gly Ser  Phe Ser Gln Pro Leu  Tyr Arg Gly Glu Leu  Asn Glu His 
    1730                 1735                 1740             


Leu Gly  Leu Leu Gly Pro Tyr  Ile Arg Ala Glu Val  Glu Asp Asn 
    1745                 1750                 1755             


Ile Met  Val Thr Phe Lys Asn  Gln Ala Ser Arg Pro  Tyr Ser Phe 
    1760                 1765                 1770             


Tyr Ser  Ser Leu Ile Ser Tyr  Lys Glu Asp Gln Arg  Gly Glu Glu 
    1775                 1780                 1785             


Pro Arg  Arg Asn Phe Val Lys  Pro Asn Glu Thr Lys  Ile Tyr Phe 
    1790                 1795                 1800             


Trp Lys  Val Gln His His Met  Ala Pro Thr Glu Asp  Glu Phe Asp 
    1805                 1810                 1815             


Cys Lys  Ala Trp Ala Tyr Phe  Ser Asp Val Asp Leu  Glu Arg Asp 
    1820                 1825                 1830             


Met His  Ser Gly Leu Ile Gly  Pro Leu Leu Ile Cys  His Ala Asn 
    1835                 1840                 1845             


Thr Leu  Asn Pro Ala His Gly  Arg Gln Val Ser Val  Gln Glu Phe 
    1850                 1855                 1860             


Ala Leu  Leu Phe Thr Ile Phe  Asp Glu Thr Lys Ser  Trp Tyr Phe 
    1865                 1870                 1875             


Thr Glu  Asn Val Lys Arg Asn  Cys Lys Thr Pro Cys  Asn Phe Gln 
    1880                 1885                 1890             


Met Glu  Asp Pro Thr Leu Lys  Glu Asn Tyr Arg Phe  His Ala Ile 
    1895                 1900                 1905             


Asn Gly  Tyr Val Met Asp Thr  Leu Pro Gly Leu Val  Met Ala Gln 
    1910                 1915                 1920             


Asp Gln  Arg Ile Arg Trp Tyr  Leu Leu Ser Met Gly  Asn Asn Glu 
    1925                 1930                 1935             


Asn Ile  Gln Ser Ile His Phe  Ser Gly His Val Phe  Thr Val Arg 
    1940                 1945                 1950             


Lys Lys  Glu Glu Tyr Lys Met  Ala Val Tyr Asn Leu  Tyr Pro Gly 
    1955                 1960                 1965             


Val Phe  Glu Thr Leu Glu Met  Ile Pro Ser Arg Ala  Gly Ile Trp 
    1970                 1975                 1980             


Arg Val  Glu Cys Leu Ile Gly  Glu His Leu Gln Ala  Gly Met Ser 
    1985                 1990                 1995             


Thr Leu  Phe Leu Val Tyr Ser  Lys Gln Cys Gln Ile  Pro Leu Gly 
    2000                 2005                 2010             


Met Ala  Ser Gly Ser Ile Arg  Asp Phe Gln Ile Thr  Ala Ser Gly 
    2015                 2020                 2025             


His Tyr  Gly Gln Trp Ala Pro  Asn Leu Ala Arg Leu  His Tyr Ser 
    2030                 2035                 2040             


Gly Ser  Ile Asn Ala Trp Ser  Thr Lys Glu Pro Phe  Ser Trp Ile 
    2045                 2050                 2055             


Lys Val  Asp Leu Leu Ala Pro  Met Ile Val His Gly  Ile Lys Thr 
    2060                 2065                 2070             


Gln Gly  Ala Arg Gln Lys Phe  Ser Ser Leu Tyr Ile  Ser Gln Phe 
    2075                 2080                 2085             


Ile Ile  Met Tyr Ser Leu Asp  Gly Lys Lys Trp Leu  Ser Tyr Gln 
    2090                 2095                 2100             


Gly Asn  Ser Thr Gly Thr Leu  Met Val Phe Phe Gly  Asn Val Asp 
    2105                 2110                 2115             


Ser Ser  Gly Ile Lys His Asn  Ser Phe Asn Pro Pro  Ile Ile Ala 
    2120                 2125                 2130             


Arg Tyr  Ile Arg Leu His Pro  Thr His Ser Ser Ile  Arg Ser Thr 
    2135                 2140                 2145             


Leu Arg  Met Glu Leu Met Gly  Cys Asp Leu Asn Ser  Cys Ser Ile 
    2150                 2155                 2160             


Pro Leu  Gly Met Glu Ser Lys  Val Ile Ser Asp Thr  Gln Ile Thr 
    2165                 2170                 2175             


Ala Ser  Ser Tyr Phe Thr Asn  Met Phe Ala Thr Trp  Ser Pro Ser 
    2180                 2185                 2190             


Gln Ala  Arg Leu His Leu Gln  Gly Arg Thr Asn Ala  Trp Arg Pro 
    2195                 2200                 2205             


Gln Val  Asn Asp Pro Lys Gln  Trp Leu Gln Val Asp  Leu Gln Lys 
    2210                 2215                 2220             


Thr Met  Lys Val Thr Gly Ile  Ile Thr Gln Gly Val  Lys Ser Leu 
    2225                 2230                 2235             


Phe Thr  Ser Met Phe Val Lys  Glu Phe Leu Ile Ser  Ser Ser Gln 
    2240                 2245                 2250             


Asp Gly  His His Trp Thr Gln  Ile Leu Tyr Asn Gly  Lys Val Lys 
    2255                 2260                 2265             


Val Phe  Gln Gly Asn Gln Asp  Ser Ser Thr Pro Met  Met Asn Ser 
    2270                 2275                 2280             


Leu Asp  Pro Pro Leu Leu Thr  Arg Tyr Leu Arg Ile  His Pro Gln 
    2285                 2290                 2295             


Ile Trp  Glu His Gln Ile Ala  Leu Arg Leu Glu Ile  Leu Gly Cys 
    2300                 2305                 2310             


Glu Ala  Gln Gln Gln Tyr 
    2315                 


<210>  15
<211>  38
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  mF8 DNA in NSA HemA mice

<400>  15
gccatcagaa gatactacct tggtggaatt gtcctgga                               38


<210>  16
<211>  38
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  mF8 DNA in NSA HemA mice with indel mutation +5

<400>  16
gccatcagaa gatactacct tggggtggtg gaattgtc                               38


<210>  17
<211>  37
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  mF8 DNA in NSA HemA mice with indel mutation -1

<400>  17
gccatcagaa gatactacct ggtggaattg tcctgga                                37


