﻿                         序列表

<110>  中国医学科学院阜外医院
 
<120>  遗传工程化的非人类哺乳动物及其构建方法和应用

<130>  P2018TC477

<160>  16    

<170>  PatentIn version 3.5

<210>  1
<211>  1040
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  ApoE gene 5' upstream to intron 1

<400>  1
aatgaggtgt ccgctccctt tgttggcggg ggaggggagc ggggggtcac aaggcatcca       60

aactccacct ctttcctctg ccctgctgtg aagggggaga gaacaacccg cctcgtgaca      120

gggggctggc acagcccgcc ctagccctga ggagggggcg ggacaggggg agtcctataa      180

ttggaccggt ctgggatccg atcccctgct cagaccctgg aggctaagga cttgtttcgg      240

aaggagctgg taagacaagc tgggctgggg attcacccag ggaccttggt aggatgtggg      300

ctgggaacct tgagatcccc cggagtccag gaaacaggca caagaattgg aaaagcaggc      360

agcacgatag aagtcttggg ggacaaacta aggactcgag gtaactagcc tttgccagag      420

tcagagcagg tggaggggtt acctccagga aggagtacgg gactgtcggt gcacggcgta      480

ccggctcaac taggaaccat cctatggcga aagaagttcc tattctctag aaagtatagg      540

aacttcaaac tcgggatgag ccttaggctg cttttatata aatacctact gatttccatc      600

acagtcccca agtaacccgg actggtttca aactgtggct cctcatggct gagctcccta      660

agttctgtag ttgtgggagg gtaccacttc gcagggatgg aggacgatta aaaatcgtgt      720

taaattaaca caaaatggaa agcaggactt agccgggaag aaagaggaat gtaagctgga      780

ccacccgctg gccctctgtg aagtggaatt tgaaccctag gagagggagc tggaattttt      840

ggcagcggat ccaccccggg gtgccgagat agcgaactcg gcaaggggag gtaaacagac      900

ctttgggaag agcgggtgct ctgttttgga gatgtttgtg atggctcaca gatctgagaa      960

gggaagatgg ggttctctgg gtggccggag tccctccacc cccgccccct ggtgttcaaa     1020

gacaattttt ccctccgcag                                                 1040


<210>  2
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  ApoE gene extron 2 part

<400>  2
actggccaat cacaattgcg aag                                               23


<210>  3
<211>  372
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  DM-PDZK1-flag

<400>  3
atggcctcca ccttcaaccc cagagagtgt aaattgtcca aacaagaggg gcagaactat       60

ggcttctttc tccgaattga gaaggacact gatggtcacc tgatccgggt gattgaggag      120

gggagcccag cagagaaggc ggggctcctg gacggtgaca gggtgctcag gatcaatggt      180

gtctttgtcg acaaggagga gcatgcgcag gtggtggagc tggtcagaaa gagtgggaat      240

tcagtgactc tgctggtcct ggatggagac tcctatgaga aggctgtgaa aaatcaggtg      300

gatttgaaag agctggatca aagccagagg gaggccgctc tgaatgatta caaggatgac      360

gacgataagt aa                                                          372


<210>  4
<211>  134
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Sh-m-SR-BI

<400>  4
cctggaggct tgctgaaggc tgtatgctga ataatcgatc ttgctgagtc gttttggcca       60

ctgactgacg actcagcgat cgattattca ggacacaagg cctgttacta gcactcacat      120

ggaacaaatg gccc                                                        134


<210>  5
<211>  718
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Gau-AngII

<400>  5
ttcattttat gtttcaggtt cagggggagg tgtgggaggt tttttaaagc aagtaaaacc       60

tctacaaatg tggtatggct gattatgatc ctctagacat atgttagaag gggtggatgt      120

atacgcggtc cctctttctt cgggcaggct tggccacctc atggtcgccg ccggccccct      180

tgatcttgtc cacctggccc tggatcttgc tggcaaaggt cgcacagcgt tgcggcagcc      240

acttcttgag caggtcagaa cactgcacgt tggcaagccc tttgaggcag ccagttgtgc      300

agtccacaca cagatcgacc tgtgcgatga actgctccat gggctccaag tccttgaacc      360

caggaatctc aggaatgtcg acgatcgcct cgcctatgcc gccctgtgcg gactctttgt      420

cgccttcgta ggtgtggcag cgtcctggga tgaacttctt catcttgggc gtgcacttga      480

tgtgggacag gcagatcaga cagcccctgg tgcagccagc tttccgggca ttggcttcca      540

tctctttgag cacctccagc ggcagcttct tgccgggcaa cttcccgcgg tcagcatcga      600

gatccgtggt cgcgaagttg ctggccacgg ccacgatgtt gaagtcttcg ttgttctcgg      660

tgggcttggc ctcggccaca gcgatgcaga tcagggcaaa cagaactttg actcccat        718


<210>  6
<211>  395
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  ApoE gene extron 4 part

<400>  6
caagggctgg ttcgagccaa tagtggaaga catgcatcgc cagtgggcaa acctgatgga       60

gaagatacag gcctctgtgg ctaccaaccc catcatcacc ccagtggccc aggagaatca      120

atgagtatcc ttctcctgtc ctgcaacaac atccatatcc agccaggtgg ccctgtctca      180

agcacctctc tggccctctg gtggcccttg cttaataaag attctccgag cacattctga      240

gtctctgtga gtgattccaa tcagcttcag cctcagttta ttgttttttg ccttacctag      300

cacacattcc atggccctgt cactatctgt agagggaggt ggttttgcag caatagaaat      360

gaagcctagg acctagcaac ataaaagaac aagtg                                 395


<210>  7
<211>  167
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  ApoE gene extron 4 downstream

<400>  7
atctaccact gagccacgcc cacagcccct cactggggga ttctaggcag gggctctacc       60

actgagccac ccgcagcccc tcactgggga atcatatcta ccactgagtc acgcccctcc      120

agcccctcac tacgggaatt ctagtcagta gctctaccac tgagcca                    167


<210>  8
<211>  3414
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  X sequence

<400>  8
atggcctcca ccttcaaccc cagagagtgt aaattgtcca aacaagaggg gcagaactat       60

ggcttctttc tccgaattga gaaggacact gatggtcacc tgatccgggt gattgaggag      120

gggagcccag cagagaaggc ggggctcctg gacggtgaca gggtgctcag gatcaatggt      180

gtctttgtcg acaaggagga gcatgcgcag gtggtggagc tggtcagaaa gagtgggaat      240

tcagtgactc tgctggtcct ggatggagac tcctatgaga aggctgtgaa aaatcaggtg      300

gatttgaaag agctggatca aagccagagg gaggccgctc tgaatgatga ttacaaggat      360

gacgacgata agtaacctgg aggcttgctg aaggctgtat gctgaataat cgatcttgct      420

gagtcgtttt ggccactgac tgacgactca gcgatcgatt attcaggaca caaggcctgt      480

tactagcact cacatggaac aaatggcccc tgtgccttct agttgccagc catctgttgt      540

ttgcccctcc cccgtgcctt ccttgaccct ggaaggtgcc actcccactg tcctttccta      600

ataaaatgag gaaattgcat cgcattgtct gagtaggtgt cattctattc tggggggtgg      660

ggtggggcag gacagcaagg gggaggattg ggaagacaat agcaggcatg ctggggatgc      720

ggtgggctct atgggaagtt cctattctct agaaagtata ggaacttcac gtcggcagtg      780

aaaaaaatgc tttatttgtg aaatttgtga tgctattgct ttatttgtaa ccattataag      840

ctgcaataaa caagttaaca acaacaattg cattcatttt atgtttcagg ttcaggggga      900

ggtgtgggag gttttttaaa gcaagtaaaa cctctacaaa tgtggtatgg ctgattatga      960

tcctctagac atatgttaga aggggtggat gtatacgcgg tccctctttc ttcgggcagg     1020

cttggccacc tcatggtcgc cgccggcccc cttgatcttg tccacctggc cctggatctt     1080

gctggcaaag gtcgcacagc gttgcggcag ccacttcttg agcaggtcag aacactgcac     1140

gttggcaagc cctttgaggc agccagttgt gcagtccaca cacagatcga cctgtgcgat     1200

gaactgctcc atgggctcca agtccttgaa cccaggaatc tcaggaatgt cgacgatcgc     1260

ctcgcctatg ccgccctgtg cggactcttt gtcgccttcg taggtgtggc agcgtcctgg     1320

gatgaacttc ttcatcttgg gcgtgcactt gatgtgggac aggcagatca gacagcccct     1380

ggtgcagcca gctttccggg cattggcttc catctctttg agcacctcca gcggcagctt     1440

cttgccgggc aacttcccgc ggtcagcatc gagatccgtg gtcgcgaagt tgctggccac     1500

ggccacgatg ttgaagtctt cgttgttctc ggtgggcttg gcctcggcca cagcgatgca     1560

gatcagggca aacagaactt tgactcccat ggtgtttacg agggtaggaa gtggtacgga     1620

aagttggtat aagacaaaag tgttgtggaa ttgaagttta ctcaaaaaat cagcactctt     1680

ttataggcgc cctggtttac ataagcaaag cttatacgtt ctctatcact gatagggagt     1740

aaactggata tacgttctct atcactgata gggagtaaac tgtagatacg ttctctatca     1800

ctgataggga gtaaactggt catacgttct ctatcactga tagggagtaa actccttata     1860

cgttctctat cactgatagg gagtaaagtc tgcatacgtt ctctatcact gatagggagt     1920

aaactcttca tacgttctct atcactgata gggagtaaac tcgagagaga aatgttctgg     1980

cacctgcact tgcactgggg acagcctatt ttgctagttt gttttgtttc gttttgtttt     2040

gatggagagc gtatgttagt actatcgatt cacacaaaaa accaacacac agatgtaatg     2100

aaaataaaga tattttattc tcgaggtgat aattccacgg ggttggggtt gcgccttttc     2160

caaggcagcc ctgggtttgc gcagggacgc ggctgctctg ggcgtggttc cgggaaacgc     2220

agcggcgccg accctgggtc tcgcacattc ttcacgtccg ttcgcagcgt cacccggatc     2280

ttcgccgcta cccttgtggg ccccccggcg acgcttcctg ctccgcccct aagtcgggaa     2340

ggttccttgc ggttcgcggc gtgccggacg tgacaaacgg aagccgcacg tctcactagt     2400

accctcgcag acggacagcg ccagggagca atggcagcgc gccgaccgcg atgggctgtg     2460

gccaatagcg gctgctcagc agggcgcgcc gagagcagcg gccgggaagg ggcggtgcgg     2520

gaggcggggt gtggggcggt agtgtgggcc ctgttcctgc ccgcgcggtg ttccgcattc     2580

tgcaagcctc cggagcgcac gtcggcagtc ggctccctcg ttgaccgaat caccgacctc     2640

tctccccagg gggatcatcg aattaccatg tctagactgg acaagagcaa agtcataaac     2700

tctgctctgg aattactcaa tggagtcggt atcgaaggcc tgacgacaag gaaactcgct     2760

caaaagctgg gagttgagca gcctaccctg tactggcacg tgaagaacaa gcgggccctg     2820

ctcgatgccc tgccaatcga gatgctggac aggcatcata cccactcctg ccccctggaa     2880

ggcgagtcat ggcaagactt tctgcggaac aacgccaagt cataccgctg tgctctcctc     2940

tcacatcgcg acggggctaa agtgcatctc ggcacccgcc caacagagaa acagtacgaa     3000

accctggaaa atcagctcgc gttcctgtgt cagcaaggct tctccctgga gaacgcactg     3060

tacgctctgt ccgccgtggg ccactttaca ctgggctgcg tattggagga acaggagcat     3120

caagtagcaa aagaggaaag agagacacct accaccgatt ctatgccccc acttctgaaa     3180

caagcaattg agctgttcga ccggcaggga gccgaacctg ccttcctttt cggcctggaa     3240

ctaatcatat gtggcctgga gaaacagcta aagtgcgaaa gcggcgggcc gaccgacgcc     3300

cttgacgatt ttgacttaga catgctccca gccgatgccc ttgacgactt tgaccttgat     3360

atgctgcctg ctgacgctct tgacgatttt gaccttgaca tgctccccgg gtaa           3414


<210>  9
<211>  116
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence of PDZK1

<400>  9

Met Ala Ser Thr Phe Asn Pro Arg Glu Cys Lys Leu Ser Lys Gln Glu 
1               5                   10                  15      


Gly Gln Asn Tyr Gly Phe Phe Leu Arg Ile Glu Lys Asp Thr Asp Gly 
            20                  25                  30          


His Leu Ile Arg Val Ile Glu Glu Gly Ser Pro Ala Glu Lys Ala Gly 
        35                  40                  45              


Leu Leu Asp Gly Asp Arg Val Leu Arg Ile Asn Gly Val Phe Val Asp 
    50                  55                  60                  


Lys Glu Glu His Ala Gln Val Val Glu Leu Val Arg Lys Ser Gly Asn 
65                  70                  75                  80  


Ser Val Thr Leu Leu Val Leu Asp Gly Asp Ser Tyr Glu Lys Ala Val 
                85                  90                  95      


Lys Asn Gln Val Asp Leu Lys Glu Leu Asp Gln Ser Gln Arg Glu Ala 
            100                 105                 110         


Ala Leu Asn Asp 
        115     


<210>  10
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence of AngII

<400>  10

Glu Gly Val Asp Val Tyr Ala Val 
1               5               


<210>  11
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  primer

<400>  11
gaaaccagtc cgggttactt ggg                                               23


<210>  12
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  primer

<400>  12
gacccagcaa atacgcctgc agg                                               23


<210>  13
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  primer

<400>  13
ggaaggagta cgggactgtc g                                                 21


<210>  14
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  primer

<400>  14
agaggagcag aaaaagcggc                                                   20


<210>  15
<211>  22
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  primer

<400>  15
atcatcattc agagcggcct cc                                                22


<210>  16
<211>  4140
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  cas9

<400>  16
atggccagca gcccccccaa gaagaagcgc aaggtcgaca agaagtactc catcggcctg       60

gacatcggca cgaacagcgt gggctgggcc gtgatcaccg acgagtacaa ggtgccgtcc      120

aagaagttca aggtgctggg caacaccgac cgccacagca tcaagaagaa cctgatcggc      180

gccctgctgt tcgactcggg cgagaccgcc gaggcgacgc gcctgaagcg caccgcgcgc      240

cgccgctaca cgcgccgcaa gaaccgcatc tgctacctgc aggagatctt cagcaacgag      300

atggccaagg tggacgactc gttcttccac cgcctggagg agtccttcct ggtggaggag      360

gacaagaagc acgagcgcca ccccatcttc ggcaacatcg tggacgaggt ggcctaccac      420

gagaagtacc cgacgatcta ccacctgcgc aagaagctgg tggacagcac cgacaaggcg      480

gacctgcgcc tgatctacct ggccctggcg cacatgatca agttccgcgg ccacttcctg      540

atcgagggcg acctgaaccc cgacaactcg gacgtggaca agctgttcat ccagctggtg      600

cagacctaca accagctgtt cgaggagaac ccgatcaacg cctcgggcgt ggacgccaag      660

gcgatcctgt ccgcgcgcct gtccaagagc cgccgcctgg agaacctgat cgcccagctg      720

cccggcgaga agaagaacgg cctgttcggc aacctgatcg cgctgagcct gggcctgacg      780

ccgaacttca agtcgaactt cgacctggcc gaggacgcga agctgcagct gagcaaggac      840

acctacgacg acgacctgga caacctgctg gcccagatcg gcgaccagta cgcggacctg      900

ttcctggccg cgaagaacct gtcggacgcc atcctgctgt ccgacatcct gcgcgtgaac      960

accaagatca cgaaggcccc cctgtcggcg tccatgatca agcgctacga cgagcaccac     1020

caggacctga ccctgctgaa ggcgctggtg cgccagcagc tgccggagaa gtacaaggag     1080

atcttcttcg accagtccaa gaacggctac gccggctaca tcgacggcgg cgccagccag     1140

gaggagttct acaagttcat caagcccatc ctggagaaga tggacggcac ggaggagctg     1200

ctggtgaagc tgaaccgcga ggacctgctg cgcaagcagc gcaccttcga caacggcagc     1260

atcccccacc agatccacct gggcgagctg cacgccatcc tgcgccgcca ggaggacttc     1320

tacccgttcc tgaaggacaa ccgcgagaag atcgagaaga tcctgacgtt ccgcatcccc     1380

tactacgtgg gcccgctggc tcgcggcaac tcccgcttcg cgtggatgac ccgcaagagc     1440

gaggagacca tcacgccctg gaacttcgag gaggtggtgg acaagggcgc cagcgcgcag     1500

tcgttcatcg agcgcatgac caacttcgac aagaacctgc ccaacgagaa ggtgctgccg     1560

aagcactccc tgctgtacga gtacttcacc gtgtacaacg agctgacgaa ggtgaagtac     1620

gtgaccgagg gcatgcgcaa gcccgccttc ctgagcggcg agcagaagaa ggcgatcgtg     1680

gacctgctgt tcaagaccaa ccgcaaggtg acggtgaagc agctgaagga ggactacttc     1740

aagaagatcg agtgcttcga cagcgtggag atctcgggcg tggaggaccg cttcaacgcc     1800

agcctgggca cctaccacga cctgctgaag atcatcaagg acaaggactt cctggacaac     1860

gaggagaacg aggacatcct ggaggacatc gtgctgaccc tgacgctgtt cgaggaccgc     1920

gagatgatcg aggagcgcct gaagacgtac gcccacctgt tcgacgacaa ggtgatgaag     1980

cagctgaagc gccgccgcta caccggctgg ggccgcctga gccgcaagct gatcaacggc     2040

atccgcgaca agcagtcggg caagaccatc ctggacttcc tgaagtccga cggcttcgcg     2100

aaccgcaact tcatgcagct gatccacgac gactcgctga ccttcaagga ggacatccag     2160

aaggcccagg tgtcgggcca gggcgactcc ctgcacgagc acatcgccaa cctggcgggc     2220

tcccccgcga tcaagaaggg catcctgcag accgtgaagg tggtggacga gctggtgaag     2280

gtgatgggcc gccacaagcc ggagaacatc gtgatcgaga tggcccgcga gaaccagacc     2340

acgcagaagg gccagaagaa cagccgcgag cgcatgaagc gcatcgagga gggcatcaag     2400

gagctgggct cgcagatcct gaaggagcac cccgtggaga acacccagct gcagaacgag     2460

aagctgtacc tgtactacct gcagaacggc cgcgacatgt acgtggacca ggagctggac     2520

atcaaccgcc tgtccgacta cgacgtggac cacatcgtgc cccagagctt cctgaaggac     2580

gactcgatcg acaacaaggt gctgacccgc agcgacaaga accgcggcaa gagcgacaac     2640

gtgccgtcgg aggaggtggt gaagaagatg aagaactact ggcgccagct gctgaacgcc     2700

aagctgatca cgcagcgcaa gttcgacaac ctgaccaagg ccgagcgcgg cggcctgtcg     2760

gagctggaca aggcgggctt catcaagcgc cagctggtgg agacccgcca gatcacgaag     2820

cacgtggcgc agatcctgga ctcccgcatg aacacgaagt acgacgagaa cgacaagctg     2880

atccgcgagg tgaaggtgat caccctgaag tccaagctgg tcagcgactt ccgcaaggac     2940

ttccagttct acaaggtgcg cgagatcaac aactaccacc acgcccacga cgcgtacctg     3000

aacgccgtgg tgggcaccgc gctgatcaag aagtacccca agctggagag cgagttcgtg     3060

tacggcgact acaaggtgta cgacgtgcgc aagatgatcg ccaagtcgga gcaggagatc     3120

ggcaaggcca ccgcgaagta cttcttctac tccaacatca tgaacttctt caagaccgag     3180

atcacgctgg ccaacggcga gatccgcaag cgccccctga tcgagaccaa cggcgagacg     3240

ggcgagatcg tgtgggacaa gggccgcgac ttcgcgaccg tgcgcaaggt gctgagcatg     3300

ccccaggtga acatcgtgaa gaagaccgag gtgcagacgg gcggcttctc caaggagagc     3360

atcctgccga agcgcaactc ggacaagctg atcgcccgca agaaggactg ggaccccaag     3420

aagtacggcg gcttcgactc cccgaccgtg gcctacagcg tgctggtggt ggcgaaggtg     3480

gagaagggca agtccaagaa gctgaagagc gtgaaggagc tgctgggcat caccatcatg     3540

gagcgcagct cgttcgagaa gaaccccatc gacttcctgg aggcgaaggg ctacaaggag     3600

gtgaagaagg acctgatcat caagctgccg aagtactcgc tgttcgagct ggagaacggc     3660

cgcaagcgca tgctggcctc cgcgggcgag ctgcagaagg gcaacgagct ggccctgccc     3720

agcaagtacg tgaacttcct gtacctggcg tcccactacg agaagctgaa gggctcgccg     3780

gaggacaacg agcagaagca gctgttcgtg gagcagcaca agcactacct ggacgagatc     3840

atcgagcaga tctcggagtt ctccaagcgc gtgatcctgg ccgacgcgaa cctggacaag     3900

gtgctgagcg cctacaacaa gcaccgcgac aagcccatcc gcgagcaggc ggagaacatc     3960

atccacctgt tcaccctgac gaacctgggc gccccggccg cgttcaagta cttcgacacc     4020

acgatcgacc gcaagcgcta caccagcacg aaggaggtgc tggacgcgac cctgatccac     4080

cagagcatca ccggcctgta cgagacgcgc atcgacctgt cgcagctggg cggcgactaa     4140



