                         SEQUENCE LISTING

<110>  UNIVERSITE CATHOLIQUE DE LOUVAIN
       Gianello, Pierre
 
<120>  TRANSGENIC PIG ISLETS AND USES THEREOF FOR TREATING DIABETES

<130>  CV - 308/PCT 

<160>  23    

<170>  PatentIn version 3.5

<210>  1
<211>  590
<212>  PRT
<213>  Sus scrofa

<400>  1

Met Thr Leu His Asn Asn Asn Thr Thr Ser Pro Leu Phe Pro Asn Ile 
1               5                   10                  15      


Ser Ser Ser Trp Ile His Gly Pro Ser Asp Ala Gly Leu Pro Pro Gly 
            20                  25                  30          


Thr Val Thr His Phe Gly Ser Tyr Asn Ile Ser Gln Ala Ala Gly Asn 
        35                  40                  45              


Phe Ser Ser Pro Asn Gly Thr Thr Ser Asp Pro Leu Gly Gly His Thr 
    50                  55                  60                  


Ile Trp Gln Val Val Phe Ile Ala Phe Leu Thr Gly Ile Leu Ala Leu 
65                  70                  75                  80  


Val Thr Ile Ile Gly Asn Ile Leu Val Ile Val Ala Phe Lys Val Asn 
                85                  90                  95      


Lys Gln Leu Lys Thr Val Asn Asn Tyr Phe Leu Leu Ser Leu Ala Cys 
            100                 105                 110         


Ala Asp Leu Ile Ile Gly Val Ile Ser Met Asn Leu Phe Thr Thr Tyr 
        115                 120                 125             


Ile Ile Met Asn Arg Trp Ala Leu Gly Asn Leu Ala Cys Asp Leu Trp 
    130                 135                 140                 


Leu Ser Ile Asp Tyr Val Ala Ser Asn Ala Ser Val Met Asn Leu Leu 
145                 150                 155                 160 


Val Ile Ser Phe Asp Arg Tyr Phe Ser Ile Thr Arg Pro Leu Thr Tyr 
                165                 170                 175     


Arg Ala Lys Arg Thr Thr Lys Arg Ala Gly Val Met Ile Gly Leu Ala 
            180                 185                 190         


Trp Val Ile Ser Phe Ile Leu Trp Ala Pro Ala Ile Leu Phe Trp Gln 
        195                 200                 205             


Tyr Phe Val Gly Lys Arg Thr Val Pro Pro Gly Glu Cys Phe Ile Gln 
    210                 215                 220                 


Phe Leu Ser Glu Pro Thr Ile Thr Phe Gly Thr Ala Ile Ala Ala Phe 
225                 230                 235                 240 


Tyr Met Pro Val Thr Ile Met Thr Ile Leu Tyr Trp Arg Ile Tyr Lys 
                245                 250                 255     


Glu Thr Glu Lys Arg Thr Lys Glu Leu Ala Gly Leu Gln Ala Ser Gly 
            260                 265                 270         


Thr Glu Ala Glu Ala Glu Asn Phe Val His Pro Thr Gly Ser Ser Arg 
        275                 280                 285             


Ser Cys Ser Ser Tyr Glu Leu Gln Gln Gln Ser Leu Lys Arg Ser Ala 
    290                 295                 300                 


Arg Arg Lys Tyr Gly Arg Cys His Phe Trp Phe Thr Thr Lys Ser Trp 
305                 310                 315                 320 


Lys Pro Ser Ala Glu Gln Met Asp Gln Asp His Ser Ser Ser Asp Ser 
                325                 330                 335     


Trp Asn Asn Asn Asp Ala Ala Ala Ser Leu Glu Asn Ser Ala Ser Ser 
            340                 345                 350         


Asp Glu Glu Asp Ile Gly Ser Glu Thr Arg Ala Ile Tyr Ser Ile Val 
        355                 360                 365             


Leu Lys Leu Pro Gly His Ser Thr Ile Leu Asn Ser Thr Lys Leu Pro 
    370                 375                 380                 


Ser Ser Asp Asn Leu Gln Val Pro Glu Glu Glu Leu Gly Thr Val Asp 
385                 390                 395                 400 


Leu Glu Arg Lys Ala Ser Lys Leu Gln Ala Gln Lys Ser Met Asp Asp 
                405                 410                 415     


Gly Gly Ser Phe Gln Lys Ser Phe Ser Lys Leu Pro Ile Gln Leu Glu 
            420                 425                 430         


Ser Ala Val Asp Thr Ala Lys Ala Ser Asp Val Asn Ser Ser Val Gly 
        435                 440                 445             


Lys Thr Thr Ala Thr Leu Pro Leu Ser Phe Lys Glu Ala Thr Leu Ala 
    450                 455                 460                 


Lys Arg Phe Ala Leu Lys Thr Arg Ser Gln Ile Thr Lys Arg Lys Arg 
465                 470                 475                 480 


Met Ser Leu Ile Lys Glu Lys Lys Ala Ala Gln Thr Leu Ser Ala Ile 
                485                 490                 495     


Leu Leu Ala Phe Ile Ile Thr Trp Thr Pro Tyr Asn Ile Met Val Leu 
            500                 505                 510         


Val Asn Thr Phe Cys Asp Ser Cys Ile Pro Lys Thr Tyr Trp Asn Leu 
        515                 520                 525             


Gly Tyr Trp Leu Cys Tyr Ile Asn Ser Thr Val Asn Pro Val Cys Tyr 
    530                 535                 540                 


Ala Leu Cys Asn Lys Thr Phe Arg Thr Thr Phe Lys Met Leu Leu Leu 
545                 550                 555                 560 


Cys Gln Cys Asp Lys Arg Lys Arg Arg Lys Gln Gln Tyr Gln Gln Arg 
                565                 570                 575     


Gln Ser Val Ile Phe His Lys Arg Val Pro Glu Gln Ala Leu 
            580                 585                 590 


<210>  2
<211>  1773
<212>  DNA
<213>  Sus scrofa

<400>  2
atgaccttgc acaataacaa tacaacctca cctttgtttc caaacatcag ctcttcctgg       60

attcacggcc cttccgatgc agggctgccc ccaggaacgg ttactcattt tggcagctac      120

aacatttctc aggcagctgg gaatttctcc tctccaaatg gcaccaccag tgaccctctg      180

ggaggtcaca ccatctggca agtggtgttc attgcattct taacaggcat cctggccttg      240

gtgactatca tcggcaatat cctggtgatc gtggcattca aggtcaacaa gcaactgaag      300

acagtcaaca actacttcct cttaagtctg gcctgtgctg acctgattat cggggtcatt      360

tcaatgaatc tgtttactac ctacatcatc atgaatcgat gggctttagg gaacttggcc      420

tgtgacctct ggctttccat tgactatgtg gctagcaatg cctcggtcat gaatcttctg      480

gtcattagct ttgacaggta cttttccatc acgaggccgc tcacataccg agccaaaaga      540

acaacaaagc gagctggtgt gatgataggt ctggcttggg tcatctcctt catcctttgg      600

gctcctgcca tcttgttctg gcaatacttt gttgggaaga gaactgtccc tccaggagag      660

tgtttcatcc agttcctcag tgagcccacc atcaccttcg gcacggccat cgctgccttt      720

tatatgcctg tcaccattat gactatttta tactggagga tctataagga aactgaaaaa      780

cgtaccaaag agcttgccgg gctgcaagcc tctgggacag aggcagaggc agaaaacttt      840

gttcacccca caggtagttc tcggagctgc agcagctatg agcttcagca gcaaagcctg      900

aaacgctcag ccaggaggaa gtatggacgc tgccacttct ggttcacaac caagagctgg      960

aagcccagtg ctgagcagat ggaccaagac cacagcagca gtgacagctg gaataacaat     1020

gatgctgctg cctccctgga aaactccgcc tcctccgatg aggaggacat tggctcagaa     1080

acaagagcca tctactccat cgtgctcaag cttccaggtc acagcaccat cctcaactcc     1140

accaagttac cgtcttcaga caacctgcag gtgcccgagg aggagctggg gacagtggac     1200

ttggagagaa aagccagcaa actgcaagcc cagaagagca tggacgatgg aggcagtttt     1260

caaaaaagct tctccaagct tcccatccag ttagagtcag ccgtggacac agccaaggcc     1320

tctgatgtca actcctcagt gggtaagacc acggccactc tacctctgtc ctttaaggaa     1380

gctactctgg ccaagaggtt tgctctgaag accagaagtc agatcaccaa gcggaaacgg     1440

atgtcgctca tcaaggagaa gaaagcggcc cagaccctca gcgccatctt gcttgccttc     1500

atcatcacct ggacccccta caatatcatg gttctggtga acaccttttg tgacagctgc     1560

atacccaaaa cctattggaa tctgggctac tggctgtgct acatcaacag caccgtgaac     1620

cccgtgtgct atgccctgtg caacaaaaca ttcagaacca ctttcaagat gctgctgctg     1680

tgccagtgtg acaaaaggaa gaggcgcaag cagcagtatc agcaaagaca gtcagtcatt     1740

ttccacaagc gggtgcccga gcaggccttg tag                                  1773


<210>  3
<211>  1185
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Constitutively activated type 3 muscarinic receptor

<400>  3
atgaccttgc acaataacaa tacaacctca cctttgtttc caaacatcag ctcttcctgg       60

attcacggcc cttccgatgc agggctgccc ccaggaacgg ttactcattt tggcagctac      120

aacatttctc aggcagctgg gaatttctcc tctccaaatg gcaccaccag tgaccctctg      180

ggaggtcaca ccatctggca agtggtgttc attgcattct taacaggcat cctggccttg      240

gtgactatca tcggcaatat cctggtgatc gtggcattca aggtcaacaa gcaactgaag      300

acagtcaaca actacttcct cttaagtctg gcctgtgctg acctgattat cggggtcatt      360

tcaatgaatc tgtttactac ctacatcatc atgaatcgat gggctttagg gaacttggcc      420

tgtgacctct ggctttccat tgactatgtg gctagcaatg cctcggtcat gaatcttctg      480

gtcattagct ttgacaggta cttttccatc acgaggccgc tcacataccg agccaaaaga      540

acaacaaagc gagctggtgt gatgataggt ctggcttggg tcatctcctt catcctttgg      600

gctcctgcca tcttgttctg gcaatacttt gttgggaaga gaactgtccc tccaggagag      660

tgtttcatcc agttcctcag tgagcccacc atcaccttcg gcacggccat cgctgccttt      720

tatatgcctg tcaccattat gactatttta tactggagga tctataagga aactgaaaaa      780

cgtaccaaag agcttgccgg gctgcaagcc tctgggacag agaccagaag tcagatcacc      840

aagcggaaac ggatgtcgct catcaaggag aagaaagcgg ccctgaccct cagcgccatc      900

ttgcttgcct tcatcatcac ctggaccccc tacaatatca tggttctggt gaacaccttt      960

tgtgacagct gcatacccaa aacctattgg aatctgggct actggctgtg ctacatcaac     1020

agcaccgtga accccgtgtg ctatgccctg tgcaacaaaa cattcagaac cactttcaag     1080

atgctgctgc tgtgccagtg tgacaaaagg aagaggcgca agcagcagta tcagcaaaga     1140

cagtcagtca ttttccacaa gcgggtgccc gagcaggcct tgtag                     1185


<210>  4
<211>  394
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  constitutively activated type 3 muscarinic receptor

<400>  4

Met Thr Leu His Asn Asn Asn Thr Thr Ser Pro Leu Phe Pro Asn Ile 
1               5                   10                  15      


Ser Ser Ser Trp Ile His Gly Pro Ser Asp Ala Gly Leu Pro Pro Gly 
            20                  25                  30          


Thr Val Thr His Phe Gly Ser Tyr Asn Ile Ser Gln Ala Ala Gly Asn 
        35                  40                  45              


Phe Ser Ser Pro Asn Gly Thr Thr Ser Asp Pro Leu Gly Gly His Thr 
    50                  55                  60                  


Ile Trp Gln Val Val Phe Ile Ala Phe Leu Thr Gly Ile Leu Ala Leu 
65                  70                  75                  80  


Val Thr Ile Ile Gly Asn Ile Leu Val Ile Val Ala Phe Lys Val Asn 
                85                  90                  95      


Lys Gln Leu Lys Thr Val Asn Asn Tyr Phe Leu Leu Ser Leu Ala Cys 
            100                 105                 110         


Ala Asp Leu Ile Ile Gly Val Ile Ser Met Asn Leu Phe Thr Thr Tyr 
        115                 120                 125             


Ile Ile Met Asn Arg Trp Ala Leu Gly Asn Leu Ala Cys Asp Leu Trp 
    130                 135                 140                 


Leu Ser Ile Asp Tyr Val Ala Ser Asn Ala Ser Val Met Asn Leu Leu 
145                 150                 155                 160 


Val Ile Ser Phe Asp Arg Tyr Phe Ser Ile Thr Arg Pro Leu Thr Tyr 
                165                 170                 175     


Arg Ala Lys Arg Thr Thr Lys Arg Ala Gly Val Met Ile Gly Leu Ala 
            180                 185                 190         


Trp Val Ile Ser Phe Ile Leu Trp Ala Pro Ala Ile Leu Phe Trp Gln 
        195                 200                 205             


Tyr Phe Val Gly Lys Arg Thr Val Pro Pro Gly Glu Cys Phe Ile Gln 
    210                 215                 220                 


Phe Leu Ser Glu Pro Thr Ile Thr Phe Gly Thr Ala Ile Ala Ala Phe 
225                 230                 235                 240 


Tyr Met Pro Val Thr Ile Met Thr Ile Leu Tyr Trp Arg Ile Tyr Lys 
                245                 250                 255     


Glu Thr Glu Lys Arg Thr Lys Glu Leu Ala Gly Leu Gln Ala Ser Gly 
            260                 265                 270         


Thr Glu Thr Arg Ser Gln Ile Thr Lys Arg Lys Arg Met Ser Leu Ile 
        275                 280                 285             


Lys Glu Lys Lys Ala Ala Gln Thr Leu Ser Ala Ile Leu Leu Ala Phe 
    290                 295                 300                 


Ile Ile Thr Trp Thr Pro Tyr Asn Ile Met Val Leu Val Asn Thr Phe 
305                 310                 315                 320 


Cys Asp Ser Cys Ile Pro Lys Thr Tyr Trp Asn Leu Gly Tyr Trp Leu 
                325                 330                 335     


Cys Tyr Ile Asn Ser Thr Val Asn Pro Val Cys Tyr Ala Leu Cys Asn 
            340                 345                 350         


Lys Thr Phe Arg Thr Thr Phe Lys Met Leu Leu Leu Cys Gln Cys Asp 
        355                 360                 365             


Lys Arg Lys Arg Arg Lys Gln Gln Tyr Gln Gln Arg Gln Ser Val Ile 
    370                 375                 380                 


Phe His Lys Arg Val Pro Glu Gln Ala Leu 
385                 390                 


<210>  5
<211>  93
<212>  DNA
<213>  Sus scrofa

<400>  5
catgctgaag ggacctttac cagtgatgta agttcttatt tggaaggcca agctgccaag       60

gaattcattg cttggctggt gaaaggccga gga                                    93


<210>  6
<211>  31
<212>  PRT
<213>  Sus scrofa

<400>  6

His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly 
1               5                   10                  15      


Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Gly 
            20                  25                  30      


<210>  7
<211>  60
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Ig K-chain secretion signal

<400>  7
gagacagaca cactcctgct atgggtactg ctgctctggg ttccaggttc cactggtgac       60


<210>  8
<211>  20
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Ig K-chain secretion signal

<400>  8

Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro Gly 
1               5                   10                  15      


Ser Thr Gly Asp 
            20  


<210>  9
<211>  171
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  A8S GLP-1 with Ig K-chain secretion signal

<400>  9
atggagacag acacactcct gctatgggta ctgctgctct gggttccagg ttccactggt       60

gaccggggca ggcggcattc cgaagggacc tttaccagtg atgtaagttc ttatttggaa      120

ggccaagctg ccaaggaatt cattgcttgg ctggtgaaag gccgaggata g               171


<210>  10
<211>  56
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  A8S GLP-1 with Ig K-chain secretion signal

<400>  10

Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 
1               5                   10                  15      


Gly Ser Thr Gly Asp Arg Gly Arg Arg His Ser Glu Gly Thr Phe Thr 
            20                  25                  30          


Ser Asp Val Ser Ser Tyr Leu Glu Gly Gln Ala Ala Lys Glu Phe Ile 
        35                  40                  45              


Ala Trp Leu Val Lys Gly Arg Gly 
    50                  55      


<210>  11
<211>  1496
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Pig Insulin Promoter

<400>  11
gagttcagct gagctggctc ccaggtcacc tctctgggtc ttggtgcccc cagcatctcc       60

caggctggcc ctgccctggg ggtgcccttc ccaccctgcc ctgggccttg tggagggcac      120

cctgggctca ctgggaggcg gtcggccctt tccttcccgc aggatgtaag caccagccta      180

tcttccaggc cctgcgccct ccctgggtgc ccccctccta cctccagagc cctgactcta      240

ggctcttagg atgtcggtct tggaaaactc ctactcatcc gtcaagaccc tcctgggaaa      300

acccttcctt cccagccccc caccctggat ctgtgccctt tcagcctttg aggccacaaa      360

tgaggctgtt tccaaaggtt ggaggcccct gggaagggct gacggccggc ctcctcccct      420

ccaacccctg ggccctgggc tctgccctca tccagtctcc tgccttgcac accctctcat      480

agaggccccc agatcttccc tggctgcaga cgggcctcag gaccccctgc tgtcctggga      540

agccagggcc cagctccttc ctccgcgtgg ggtggggcct ccccacaggg gcctgtcccg      600

ggggggtacc agagggtcac ccccgcacat gggacagcga agggaagcag tatgtcgtgg      660

ggccgggtct gaaaggggtc agcagcaggg gctccaggag gcaggggcac tgagcggtac      720

ctggggggga ggtggtgggg ccacacccag gagtcctgtg ccccccccac tcccgccgtt      780

ggagatgaga agcaggggcc agcctgcggg tccctgagtt cagcgcccac ccccccgccg      840

cagcaccccg gggtctcagc aggctgctgt gctgggggcg ggggcgctta tggagccggg      900

agcagccccc cccccacggc ctcggagcat ctctggggcc tcagggatgg accggggtct      960

gcaggcaggt gtcctctcgc gcccccactc cctgggctat aacgtggaag atgcggccca     1020

agcccggtcg gtttggcctt tgtccccagc cagtggggac agcctggccc tcaggctgct     1080

cgttaagact ctaatgacct cgaggccccc agaggcgctg atgacccacg gagatgatcc     1140

cgcaggcctg gcagcaggga aatgatccag aaagtgccac ctcagccccc agccatctgc     1200

cacccacctg gaggccctca ggggccgggc gccggggggc aggcgctata aagccggctg     1260

ggcccagccg cccccagccc tctgggacca gctgtgttcc caggccaccg gcaagcaggt     1320

ctgtccccct gggctcccgt cagctgggtc tgggctgtcc tgctggggcc agggcatctc     1380

ggcaggagga cgtgggctcc tctctcggag cccttggggg gtgaggctgg tgggggctgc     1440

aggtgcccct ggctggcctc aacgccgccc gtcccccagg tcctcacccc ccgccc         1496


<210>  12
<211>  27
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  HA tag

<400>  12
tacccatacg atgttccaga ttacgct                                           27


<210>  13
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  HA tag

<400>  13

Tyr Pro Tyr Asp Val Pro Asp Tyr Ala 
1               5                   


<210>  14
<211>  456
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Rabbit beta globin fragment comprising a polyA sequence

<400>  14
ctttttccct ctgccaaaaa ttatggggac atcatgaagc cccttgagca tctgacttct       60

ggctaataaa ggaaatttat tttcattgca atagtgtgtt ggaatttttt gtgtctctca      120

ctcggaagga catatgggag ggcaaatcat ttaaaacatc agaatgagta tttggtttag      180

agtttggcaa catatgccat atgctggctg ccatgaacaa aggtggctat aaagaggtca      240

tcagtatatg aaacagcccc ctgctgtcca ttccttattc catagaaaag ccttgacttg      300

aggttagatt ttttttatat tttgttttgt gttatttttt tctttaacat ccctaaaatt      360

ttccttacat gttttactag ccagattttt cctcctctcc tgactactcc cagtcatagc      420

tgtccctctt ctcttatgaa gatccctcga cctgca                                456


<210>  15
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  GLP-1 - Forward primer

<400>  15
cccgcccaat tgatggagac                                                   20


<210>  16
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  GLP-1 - Reverse primer

<400>  16
tcctcggcct ttcaccagcc                                                   20


<210>  17
<211>  20
<212>  DNA
<213>  M3R - Forward primer

<400>  17
cccaattgat gtacccatac                                                   20


<210>  18
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  M3R - Reverse Primer

<400>  18
gtgatctgac ttctggtctc                                                   20


<210>  19
<211>  93
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  A8S GLP-1

<400>  19
cattccgaag ggacctttac cagtgatgta agttcttatt tggaaggcca agctgccaag       60

gaattcattg cttggctggt gaaaggccga gga                                    93


<210>  20
<211>  31
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  A8S GLP-1

<400>  20

His Ser Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly 
1               5                   10                  15      


Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Gly 
            20                  25                  30      


<210>  21
<211>  403
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  HA-Tagged mutated type 3 muscarinic receptor

<400>  21

Met Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Thr Leu His Asn Asn Asn 
1               5                   10                  15      


Thr Thr Ser Pro Leu Phe Pro Asn Ile Ser Ser Ser Trp Ile His Gly 
            20                  25                  30          


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


Tyr Asn Ile Ser Gln Ala Ala Gly Asn Phe Ser Ser Pro Asn Gly Thr 
    50                  55                  60                  


Thr Ser Asp Pro Leu Gly Gly His Thr Ile Trp Gln Val Val Phe Ile 
65                  70                  75                  80  


Ala Phe Leu Thr Gly Ile Leu Ala Leu Val Thr Ile Ile Gly Asn Ile 
                85                  90                  95      


Leu Val Ile Val Ala Phe Lys Val Asn Lys Gln Leu Lys Thr Val Asn 
            100                 105                 110         


Asn Tyr Phe Leu Leu Ser Leu Ala Cys Ala Asp Leu Ile Ile Gly Val 
        115                 120                 125             


Ile Ser Met Asn Leu Phe Thr Thr Tyr Ile Ile Met Asn Arg Trp Ala 
    130                 135                 140                 


Leu Gly Asn Leu Ala Cys Asp Leu Trp Leu Ser Ile Asp Tyr Val Ala 
145                 150                 155                 160 


Ser Asn Ala Ser Val Met Asn Leu Leu Val Ile Ser Phe Asp Arg Tyr 
                165                 170                 175     


Phe Ser Ile Thr Arg Pro Leu Thr Tyr Arg Ala Lys Arg Thr Thr Lys 
            180                 185                 190         


Arg Ala Gly Val Met Ile Gly Leu Ala Trp Val Ile Ser Phe Ile Leu 
        195                 200                 205             


Trp Ala Pro Ala Ile Leu Phe Trp Gln Tyr Phe Val Gly Lys Arg Thr 
    210                 215                 220                 


Val Pro Pro Gly Glu Cys Phe Ile Gln Phe Leu Ser Glu Pro Thr Ile 
225                 230                 235                 240 


Thr Phe Gly Thr Ala Ile Ala Ala Phe Tyr Met Pro Val Thr Ile Met 
                245                 250                 255     


Thr Ile Leu Tyr Trp Arg Ile Tyr Lys Glu Thr Glu Lys Arg Thr Lys 
            260                 265                 270         


Glu Leu Ala Gly Leu Gln Ala Ser Gly Thr Glu Thr Arg Ser Gln Ile 
        275                 280                 285             


Thr Lys Arg Lys Arg Met Ser Leu Ile Lys Glu Lys Lys Ala Ala Gln 
    290                 295                 300                 


Thr Leu Ser Ala Ile Leu Leu Ala Phe Ile Ile Thr Trp Thr Pro Tyr 
305                 310                 315                 320 


Asn Ile Met Val Leu Val Asn Thr Phe Cys Asp Ser Cys Ile Pro Lys 
                325                 330                 335     


Thr Tyr Trp Asn Leu Gly Tyr Trp Leu Cys Tyr Ile Asn Ser Thr Val 
            340                 345                 350         


Asn Pro Val Cys Tyr Ala Leu Cys Asn Lys Thr Phe Arg Thr Thr Phe 
        355                 360                 365             


Lys Met Leu Leu Leu Cys Gln Cys Asp Lys Arg Lys Arg Arg Lys Gln 
    370                 375                 380                 


Gln Tyr Gln Gln Arg Gln Ser Val Ile Phe His Lys Arg Val Pro Glu 
385                 390                 395                 400 


Gln Ala Leu 
            


<210>  22
<211>  3169
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Constitutively activated type 3 muscarinic receptor - Vector

<400>  22
gagttcagct gagctggctc ccaggtcacc tctctgggtc ttggtgcccc cagcatctcc       60

caggctggcc ctgccctggg ggtgcccttc ccaccctgcc ctgggccttg tggagggcac      120

cctgggctca ctgggaggcg gtcggccctt tccttcccgc aggatgtaag caccagccta      180

tcttccaggc cctgcgccct ccctgggtgc ccccctccta cctccagagc cctgactcta      240

ggctcttagg atgtcggtct tggaaaactc ctactcatcc gtcaagaccc tcctgggaaa      300

acccttcctt cccagccccc caccctggat ctgtgccctt tcagcctttg aggccacaaa      360

tgaggctgtt tccaaaggtt ggaggcccct gggaagggct gacggccggc ctcctcccct      420

ccaacccctg ggccctgggc tctgccctca tccagtctcc tgccttgcac accctctcat      480

agaggccccc agatcttccc tggctgcaga cgggcctcag gaccccctgc tgtcctggga      540

agccagggcc cagctccttc ctccgcgtgg ggtggggcct ccccacaggg gcctgtcccg      600

ggggggtacc agagggtcac ccccgcacat gggacagcga agggaagcag tatgtcgtgg      660

ggccgggtct gaaaggggtc agcagcaggg gctccaggag gcaggggcac tgagcggtac      720

ctggggggga ggtggtgggg ccacacccag gagtcctgtg ccccccccac tcccgccgtt      780

ggagatgaga agcaggggcc agcctgcggg tccctgagtt cagcgcccac ccccccgccg      840

cagcaccccg gggtctcagc aggctgctgt gctgggggcg ggggcgctta tggagccggg      900

agcagccccc cccccacggc ctcggagcat ctctggggcc tcagggatgg accggggtct      960

gcaggcaggt gtcctctcgc gcccccactc cctgggctat aacgtggaag atgcggccca     1020

agcccggtcg gtttggcctt tgtccccagc cagtggggac agcctggccc tcaggctgct     1080

cgttaagact ctaatgacct cgaggccccc agaggcgctg atgacccacg gagatgatcc     1140

cgcaggcctg gcagcaggga aatgatccag aaagtgccac ctcagccccc agccatctgc     1200

cacccacctg gaggccctca ggggccgggc gccggggggc aggcgctata aagccggctg     1260

ggcccagccg cccccagccc tctgggacca gctgtgttcc caggccaccg gcaagcaggt     1320

ctgtccccct gggctcccgt cagctgggtc tgggctgtcc tgctggggcc agggcatctc     1380

ggcaggagga cgtgggctcc tctctcggag cccttggggg gtgaggctgg tgggggctgc     1440

aggtgcccct ggctggcctc aacgccgccc gtcccccagg tcctcacccc ccgcccaatt     1500

gatgtaccca tacgatgttc cagattacgc taccttgcac aataacaata caacctcacc     1560

tttgtttcca aacatcagct cttcctggat tcacggccct tccgatgcag ggctgccccc     1620

aggaacggtt actcattttg gcagctacaa catttctcag gcagctggga atttctcctc     1680

tccaaatggc accaccagtg accctctggg aggtcacacc atctggcaag tggtgttcat     1740

tgcattctta acaggcatcc tggccttggt gactatcatc ggcaatatcc tggtgatcgt     1800

ggcattcaag gtcaacaagc aactgaagac agtcaacaac tacttcctct taagtctggc     1860

ctgtgctgac ctgattatcg gggtcatttc aatgaatctg tttactacct acatcatcat     1920

gaatcgatgg gctttaggga acttggcctg tgacctctgg ctttccattg actatgtggc     1980

tagcaatgcc tcggtcatga atcttctggt cattagcttt gacaggtact tttccatcac     2040

gaggccgctc acataccgag ccaaaagaac aacaaagcga gctggtgtga tgataggtct     2100

ggcttgggtc atctccttca tcctttgggc tcctgccatc ttgttctggc aatactttgt     2160

tgggaagaga actgtccctc caggagagtg tttcatccag ttcctcagtg agcccaccat     2220

caccttcggc acggccatcg ctgcctttta tatgcctgtc accattatga ctattttata     2280

ctggaggatc tataaggaaa ctgaaaaacg taccaaagag cttgccgggc tgcaagcctc     2340

tgggacagag accagaagtc agatcaccaa gcggaaacgg atgtcgctca tcaaggagaa     2400

gaaagcggcc ctgaccctca gcgccatctt gcttgccttc atcatcacct ggacccccta     2460

caatatcatg gttctggtga acaccttttg tgacagctgc atacccaaaa cctattggaa     2520

tctgggctac tggctgtgct acatcaacag caccgtgaac cccgtgtgct atgccctgtg     2580

caacaaaaca ttcagaacca ctttcaagat gctgctgctg tgccagtgtg acaaaaggaa     2640

gaggcgcaag cagcagtatc agcaaagaca gtcagtcatt ttccacaagc gggtgcccga     2700

gcaggccttg tagctttttc cctctgccaa aaattatggg gacatcatga agccccttga     2760

gcatctgact tctggctaat aaaggaaatt tattttcatt gcaatagtgt gttggaattt     2820

tttgtgtctc tcactcggaa ggacatatgg gagggcaaat catttaaaac atcagaatga     2880

gtatttggtt tagagtttgg caacatatgc catatgctgg ctgccatgaa caaaggtggc     2940

tataaagagg tcatcagtat atgaaacagc cccctgctgt ccattcctta ttccatagaa     3000

aagccttgac ttgaggttag atttttttta tattttgttt tgtgttattt ttttctttaa     3060

catccctaaa attttcctta catgttttac tagccagatt tttcctcctc tcctgactac     3120

tcccagtcat agctgtccct cttctcttat gaagatccct cgacctgca                 3169


<210>  23
<211>  2131
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  GLP-1 - Vector

<400>  23
gagttcagct gagctggctc ccaggtcacc tctctgggtc ttggtgcccc cagcatctcc       60

caggctggcc ctgccctggg ggtgcccttc ccaccctgcc ctgggccttg tggagggcac      120

cctgggctca ctgggaggcg gtcggccctt tccttcccgc aggatgtaag caccagccta      180

tcttccaggc cctgcgccct ccctgggtgc ccccctccta cctccagagc cctgactcta      240

ggctcttagg atgtcggtct tggaaaactc ctactcatcc gtcaagaccc tcctgggaaa      300

acccttcctt cccagccccc caccctggat ctgtgccctt tcagcctttg aggccacaaa      360

tgaggctgtt tccaaaggtt ggaggcccct gggaagggct gacggccggc ctcctcccct      420

ccaacccctg ggccctgggc tctgccctca tccagtctcc tgccttgcac accctctcat      480

agaggccccc agatcttccc tggctgcaga cgggcctcag gaccccctgc tgtcctggga      540

agccagggcc cagctccttc ctccgcgtgg ggtggggcct ccccacaggg gcctgtcccg      600

ggggggtacc agagggtcac ccccgcacat gggacagcga agggaagcag tatgtcgtgg      660

ggccgggtct gaaaggggtc agcagcaggg gctccaggag gcaggggcac tgagcggtac      720

ctggggggga ggtggtgggg ccacacccag gagtcctgtg ccccccccac tcccgccgtt      780

ggagatgaga agcaggggcc agcctgcggg tccctgagtt cagcgcccac ccccccgccg      840

cagcaccccg gggtctcagc aggctgctgt gctgggggcg ggggcgctta tggagccggg      900

agcagccccc cccccacggc ctcggagcat ctctggggcc tcagggatgg accggggtct      960

gcaggcaggt gtcctctcgc gcccccactc cctgggctat aacgtggaag atgcggccca     1020

agcccggtcg gtttggcctt tgtccccagc cagtggggac agcctggccc tcaggctgct     1080

cgttaagact ctaatgacct cgaggccccc agaggcgctg atgacccacg gagatgatcc     1140

cgcaggcctg gcagcaggga aatgatccag aaagtgccac ctcagccccc agccatctgc     1200

cacccacctg gaggccctca ggggccgggc gccggggggc aggcgctata aagccggctg     1260

ggcccagccg cccccagccc tctgggacca gctgtgttcc caggccaccg gcaagcaggt     1320

ctgtccccct gggctcccgt cagctgggtc tgggctgtcc tgctggggcc agggcatctc     1380

ggcaggagga cgtgggctcc tctctcggag cccttggggg gtgaggctgg tgggggctgc     1440

aggtgcccct ggctggcctc aacgccgccc gtcccccagg tcctcacccc ccgcccaatt     1500

gatggagaca gacacactcc tgctatgggt actgctgctc tgggttccag gttccactgg     1560

tgaccggggc aggcggcatt ccgaagggac ctttaccagt gatgtaagtt cttatttgga     1620

aggccaagct gccaaggaat tcattgcttg gctggtgaaa ggccgaggat aggatctttt     1680

tccctctgcc aaaaattatg gggacatcat gaagcccctt gagcatctga cttctggcta     1740

ataaaggaaa tttattttca ttgcaatagt gtgttggaat tttttgtgtc tctcactcgg     1800

aaggacatat gggagggcaa atcatttaaa acatcagaat gagtatttgg tttagagttt     1860

ggcaacatat gccatatgct ggctgccatg aacaaaggtg gctataaaga ggtcatcagt     1920

atatgaaaca gccccctgct gtccattcct tattccatag aaaagccttg acttgaggtt     1980

agattttttt tatattttgt tttgtgttat ttttttcttt aacatcccta aaattttcct     2040

tacatgtttt actagccaga tttttcctcc tctcctgact actcccagtc atagctgtcc     2100

ctcttctctt atgaagatcc ctcgacctgc a                                    2131


