CA2193513A1 - Structures geniques d'alpha-lactalbumine - Google Patents
Structures geniques d'alpha-lactalbumineInfo
- Publication number
- CA2193513A1 CA2193513A1 CA002193513A CA2193513A CA2193513A1 CA 2193513 A1 CA2193513 A1 CA 2193513A1 CA 002193513 A CA002193513 A CA 002193513A CA 2193513 A CA2193513 A CA 2193513A CA 2193513 A1 CA2193513 A1 CA 2193513A1
- Authority
- CA
- Canada
- Prior art keywords
- lactalbumin
- milk
- human
- construct
- alpha
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 108090000942 Lactalbumin Proteins 0.000 title description 31
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 87
- 241000283690 Bos taurus Species 0.000 claims abstract description 61
- 241001465754 Metazoa Species 0.000 claims abstract description 56
- 230000009261 transgenic effect Effects 0.000 claims abstract description 41
- 239000013598 vector Substances 0.000 claims abstract description 19
- 230000002068 genetic effect Effects 0.000 claims abstract description 9
- 235000013336 milk Nutrition 0.000 claims description 81
- 210000004080 milk Anatomy 0.000 claims description 81
- 239000008267 milk Substances 0.000 claims description 80
- 238000000034 method Methods 0.000 claims description 23
- 108091033319 polynucleotide Proteins 0.000 claims description 10
- 102000040430 polynucleotide Human genes 0.000 claims description 10
- 239000002157 polynucleotide Substances 0.000 claims description 10
- 108020005029 5' Flanking Region Proteins 0.000 claims description 6
- 108020005065 3' Flanking Region Proteins 0.000 claims description 5
- 230000014509 gene expression Effects 0.000 abstract description 41
- 102000004169 proteins and genes Human genes 0.000 abstract description 31
- 235000018102 proteins Nutrition 0.000 abstract description 28
- 238000004519 manufacturing process Methods 0.000 abstract description 7
- 102000007544 Whey Proteins Human genes 0.000 abstract description 6
- 108010046377 Whey Proteins Proteins 0.000 abstract description 6
- 235000020256 human milk Nutrition 0.000 abstract description 6
- 210000004251 human milk Anatomy 0.000 abstract description 6
- 235000021119 whey protein Nutrition 0.000 abstract description 5
- 235000021125 infant nutrition Nutrition 0.000 abstract description 2
- 239000012634 fragment Substances 0.000 description 62
- 241000699666 Mus <mouse, genus> Species 0.000 description 59
- 102000004407 Lactalbumin Human genes 0.000 description 28
- 241000699670 Mus sp. Species 0.000 description 24
- 108700019146 Transgenes Proteins 0.000 description 24
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 22
- 108020004999 messenger RNA Proteins 0.000 description 20
- 238000004458 analytical method Methods 0.000 description 17
- 108020004414 DNA Proteins 0.000 description 16
- YDHOAQXHVQTASS-UHFFFAOYSA-N 3-amino-n-hydroxypropanamide Chemical compound NCCC(=O)NO YDHOAQXHVQTASS-UHFFFAOYSA-N 0.000 description 13
- 239000002299 complementary DNA Substances 0.000 description 13
- 210000005075 mammary gland Anatomy 0.000 description 13
- 238000003259 recombinant expression Methods 0.000 description 13
- 238000011830 transgenic mouse model Methods 0.000 description 13
- 108700028369 Alleles Proteins 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- 241000699660 Mus musculus Species 0.000 description 9
- 239000008101 lactose Substances 0.000 description 9
- 239000000523 sample Substances 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 8
- 239000000499 gel Substances 0.000 description 8
- 229920002684 Sepharose Polymers 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 238000000520 microinjection Methods 0.000 description 7
- 239000002773 nucleotide Substances 0.000 description 7
- 125000003729 nucleotide group Chemical group 0.000 description 7
- 241001494479 Pecora Species 0.000 description 6
- 102000006382 Ribonucleases Human genes 0.000 description 6
- 108010083644 Ribonucleases Proteins 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 102000039446 nucleic acids Human genes 0.000 description 6
- 108020004707 nucleic acids Proteins 0.000 description 6
- 150000007523 nucleic acids Chemical class 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 6
- 241000894007 species Species 0.000 description 6
- 238000001262 western blot Methods 0.000 description 6
- 108091026890 Coding region Proteins 0.000 description 5
- 108010060630 Lactoglobulins Proteins 0.000 description 5
- 210000000349 chromosome Anatomy 0.000 description 5
- 210000002257 embryonic structure Anatomy 0.000 description 5
- 210000004907 gland Anatomy 0.000 description 5
- 230000010354 integration Effects 0.000 description 5
- 230000006651 lactation Effects 0.000 description 5
- 238000011144 upstream manufacturing Methods 0.000 description 5
- 108700024394 Exon Proteins 0.000 description 4
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 4
- 102000008192 Lactoglobulins Human genes 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 238000009395 breeding Methods 0.000 description 4
- 230000001488 breeding effect Effects 0.000 description 4
- 239000005018 casein Substances 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 235000020247 cow milk Nutrition 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000009396 hybridization Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000008488 polyadenylation Effects 0.000 description 4
- 238000011002 quantification Methods 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 108091008146 restriction endonucleases Proteins 0.000 description 4
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 3
- 241000283725 Bos Species 0.000 description 3
- 241000283707 Capra Species 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 108010011756 Milk Proteins Proteins 0.000 description 3
- 241001529936 Murinae Species 0.000 description 3
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 3
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 3
- 238000012300 Sequence Analysis Methods 0.000 description 3
- 241000282887 Suidae Species 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 230000003321 amplification Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 210000001161 mammalian embryo Anatomy 0.000 description 3
- 238000005528 milk analysis Methods 0.000 description 3
- 238000003199 nucleic acid amplification method Methods 0.000 description 3
- 235000016709 nutrition Nutrition 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 235000020183 skimmed milk Nutrition 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 2
- 102100026398 Cyclic AMP-responsive element-binding protein 3 Human genes 0.000 description 2
- 101710128029 Cyclic AMP-responsive element-binding protein 3 Proteins 0.000 description 2
- 230000004543 DNA replication Effects 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- 102000014171 Milk Proteins Human genes 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 102000003992 Peroxidases Human genes 0.000 description 2
- 108020004518 RNA Probes Proteins 0.000 description 2
- 239000003391 RNA probe Substances 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 239000012491 analyte Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000008827 biological function Effects 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 238000009585 enzyme analysis Methods 0.000 description 2
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000035558 fertility Effects 0.000 description 2
- 238000010353 genetic engineering Methods 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 235000021239 milk protein Nutrition 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 210000003101 oviduct Anatomy 0.000 description 2
- 108040007629 peroxidase activity proteins Proteins 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 235000019624 protein content Nutrition 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 230000005026 transcription initiation Effects 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 238000011870 unpaired t-test Methods 0.000 description 2
- WZUVPPKBWHMQCE-XJKSGUPXSA-N (+)-haematoxylin Chemical compound C12=CC(O)=C(O)C=C2C[C@]2(O)[C@H]1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-XJKSGUPXSA-N 0.000 description 1
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- JEOQACOXAOEPLX-WCCKRBBISA-N (2s)-2-amino-5-(diaminomethylideneamino)pentanoic acid;1,3-thiazolidine-4-carboxylic acid Chemical compound OC(=O)C1CSCN1.OC(=O)[C@@H](N)CCCN=C(N)N JEOQACOXAOEPLX-WCCKRBBISA-N 0.000 description 1
- XYGVIBXOJOOCFR-BTJKTKAUSA-N (z)-but-2-enedioic acid;8-chloro-6-(2-fluorophenyl)-1-methyl-4h-imidazo[1,5-a][1,4]benzodiazepine Chemical compound OC(=O)\C=C/C(O)=O.C12=CC(Cl)=CC=C2N2C(C)=NC=C2CN=C1C1=CC=CC=C1F XYGVIBXOJOOCFR-BTJKTKAUSA-N 0.000 description 1
- UGBLISDIHDMHJX-UHFFFAOYSA-N 1-(4-fluorophenyl)-4-[4-(2-methoxyphenyl)piperazin-1-yl]butan-1-one;hydrochloride Chemical compound [Cl-].COC1=CC=CC=C1N1CC[NH+](CCCC(=O)C=2C=CC(F)=CC=2)CC1 UGBLISDIHDMHJX-UHFFFAOYSA-N 0.000 description 1
- 101150007523 32 gene Proteins 0.000 description 1
- 101150033839 4 gene Proteins 0.000 description 1
- 241000023308 Acca Species 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 108020005544 Antisense RNA Proteins 0.000 description 1
- 238000012935 Averaging Methods 0.000 description 1
- 101500014077 Bombina orientalis C-terminal extension peptide Proteins 0.000 description 1
- 101001008231 Bos taurus Beta-lactoglobulin Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282836 Camelus dromedarius Species 0.000 description 1
- 102000011632 Caseins Human genes 0.000 description 1
- 108010076119 Caseins Proteins 0.000 description 1
- 241000252095 Congridae Species 0.000 description 1
- 241000195493 Cryptophyta Species 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 241000002335 Dichotomopilus indicus Species 0.000 description 1
- 101710095439 Erlin Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 101000867232 Escherichia coli Heat-stable enterotoxin II Proteins 0.000 description 1
- 108091029865 Exogenous DNA Proteins 0.000 description 1
- 102000002464 Galactosidases Human genes 0.000 description 1
- 108010093031 Galactosidases Proteins 0.000 description 1
- 108010015776 Glucose oxidase Proteins 0.000 description 1
- 239000004366 Glucose oxidase Substances 0.000 description 1
- 102100022662 Guanylyl cyclase C Human genes 0.000 description 1
- 101710198293 Guanylyl cyclase C Proteins 0.000 description 1
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Natural products C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- 238000003744 In vitro fertilisation Methods 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- PKFBJSDMCRJYDC-GEZSXCAASA-N N-acetyl-s-geranylgeranyl-l-cysteine Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CSC[C@@H](C(O)=O)NC(C)=O PKFBJSDMCRJYDC-GEZSXCAASA-N 0.000 description 1
- 108091092724 Noncoding DNA Proteins 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 241000282320 Panthera leo Species 0.000 description 1
- 244000028344 Primula vulgaris Species 0.000 description 1
- 235000016311 Primula vulgaris Nutrition 0.000 description 1
- 101000702488 Rattus norvegicus High affinity cationic amino acid transporter 1 Proteins 0.000 description 1
- 101710146873 Receptor-binding protein Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108700005075 Regulator Genes Proteins 0.000 description 1
- 238000002105 Southern blotting Methods 0.000 description 1
- 241000890661 Sudra Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 101710137500 T7 RNA polymerase Proteins 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 108700009124 Transcription Initiation Site Proteins 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 239000005862 Whey Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 238000001949 anaesthesia Methods 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 235000008452 baby food Nutrition 0.000 description 1
- 235000013405 beer Nutrition 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 235000020248 camel milk Nutrition 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000011098 chromatofocusing Methods 0.000 description 1
- 239000013611 chromosomal DNA Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000013599 cloning vector Substances 0.000 description 1
- 239000003184 complementary RNA Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- GOHCTCOGYKAJLZ-UHFFFAOYSA-N ctep Chemical compound CC=1N(C=2C=CC(OC(F)(F)F)=CC=2)C(C)=NC=1C#CC1=CC=NC(Cl)=C1 GOHCTCOGYKAJLZ-UHFFFAOYSA-N 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000003056 effect on lactation Effects 0.000 description 1
- 238000001378 electrochemiluminescence detection Methods 0.000 description 1
- 238000005430 electron energy loss spectroscopy Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 235000019625 fat content Nutrition 0.000 description 1
- 235000013350 formula milk Nutrition 0.000 description 1
- 238000012224 gene deletion Methods 0.000 description 1
- 238000010363 gene targeting Methods 0.000 description 1
- 230000004077 genetic alteration Effects 0.000 description 1
- 231100000118 genetic alteration Toxicity 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 229940116332 glucose oxidase Drugs 0.000 description 1
- 235000019420 glucose oxidase Nutrition 0.000 description 1
- 235000020251 goat milk Nutrition 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 235000021244 human milk protein Nutrition 0.000 description 1
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 1
- 229940127121 immunoconjugate Drugs 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 230000023247 mammary gland development Effects 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 238000007431 microscopic evaluation Methods 0.000 description 1
- 235000021243 milk fat Nutrition 0.000 description 1
- ZAHQPTJLOCWVPG-UHFFFAOYSA-N mitoxantrone dihydrochloride Chemical compound Cl.Cl.O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO ZAHQPTJLOCWVPG-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 210000002445 nipple Anatomy 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 210000000287 oocyte Anatomy 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 230000001915 proofreading effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 235000020254 sheep milk Nutrition 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 235000021247 β-casein Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
- A01K67/0276—Knock-out vertebrates
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
- A01K67/0278—Knock-in vertebrates, e.g. humanised vertebrates
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
- A23C9/00—Milk preparations; Milk powder or milk powder preparations
- A23C9/20—Dietetic milk products not covered by groups A23C9/12 - A23C9/18
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/76—Albumins
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2207/00—Modified animals
- A01K2207/15—Humanized animals
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/07—Animals genetically altered by homologous recombination
- A01K2217/075—Animals genetically altered by homologous recombination inducing loss of function, i.e. knock out
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2227/00—Animals characterised by species
- A01K2227/10—Mammal
- A01K2227/101—Bovine
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2227/00—Animals characterised by species
- A01K2227/10—Mammal
- A01K2227/105—Murine
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/01—Animal expressing industrially exogenous proteins
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Environmental Sciences (AREA)
- Zoology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Veterinary Medicine (AREA)
- Organic Chemistry (AREA)
- Animal Husbandry (AREA)
- Animal Behavior & Ethology (AREA)
- Biodiversity & Conservation Biology (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Molecular Biology (AREA)
- General Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Nutrition Science (AREA)
- Physics & Mathematics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Chemistry (AREA)
- Plant Pathology (AREA)
- Gastroenterology & Hepatology (AREA)
- Microbiology (AREA)
- Toxicology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
Structures géniques recombinées destinées à exprimer dans des cellules bovines la protéine .alpha.-lactalbumine, notamment l'.alpha.-lactalbumine humaine. On décrit des nouvelles structures géniques, des vecteurs et des cellules modifiées, de même que des animaux transgéniques obtenus par génie génétique, aux fins d'une expression accrue de l'.alpha.-lactalbumine. L'.alpha.-lactalbumine humaine s'est révélée être supérieure pour la nutrition de l'enfant, et la présente invention permet d'obtenir une forme de production bon marché et efficace, dans le lait humain, de la protéine principale du petit lait.
Applications Claiming Priority (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/GB1994/001514 WO1995002692A1 (fr) | 1993-07-16 | 1994-07-13 | Alpha-lactalbumine modifiee |
| GBPCT/GB94/01514 | 1994-07-13 | ||
| GB9425326.7 | 1994-12-15 | ||
| GBGB9425326.7A GB9425326D0 (en) | 1994-12-15 | 1994-12-15 | Gene constructs |
| US08/381,691 US5852224A (en) | 1994-12-15 | 1995-01-31 | α-lactalbumin gene constructs |
| US08/381,691 | 1995-01-31 | ||
| GBGB9503822.0A GB9503822D0 (en) | 1995-02-25 | 1995-02-25 | "Alpha-lactalbumin gene constructs" |
| GB9503822.0 | 1995-02-25 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2193513A1 true CA2193513A1 (fr) | 1996-02-01 |
Family
ID=56289646
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002193513A Abandoned CA2193513A1 (fr) | 1994-07-13 | 1995-07-12 | Structures geniques d'alpha-lactalbumine |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP0765390A1 (fr) |
| JP (1) | JPH10502816A (fr) |
| CN (1) | CN1157635A (fr) |
| AU (1) | AU700224B2 (fr) |
| CA (1) | CA2193513A1 (fr) |
| NZ (1) | NZ289197A (fr) |
| WO (1) | WO1996002640A1 (fr) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100335632C (zh) * | 2000-12-08 | 2007-09-05 | 李宁 | 牦牛的七种乳蛋白基因序列 |
| CN100445379C (zh) * | 2005-04-21 | 2008-12-24 | 李宁 | 转人α-乳清蛋白基因的动物细胞的生产方法 |
| CN101104635B (zh) * | 2007-04-30 | 2010-11-03 | 北京济普霖生物技术有限公司 | 一种从转基因牛乳中纯化重组人α-乳清白蛋白的方法 |
| WO2010119088A2 (fr) * | 2009-04-15 | 2010-10-21 | Bodo Melnik | Lait et produits lactés modifiés pour présenter un indice insulinémique réduit et/ou une activité mitogène réduite |
| CN102590413B (zh) * | 2012-01-18 | 2013-12-25 | 浙江省疾病预防控制中心 | 一种牛α-乳白蛋白的定量检测方法 |
| CN114736287B (zh) * | 2022-04-20 | 2023-07-07 | 中国农业科学院生物技术研究所 | 低致敏性α-乳白蛋白及其制备方法和应用 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3670003B2 (ja) * | 1992-06-15 | 2005-07-13 | ファーミング ビー．ブイ． | ウシ種による組み換えポリペプチドの製造及びトランスジェニック法 |
| GB9314802D0 (en) * | 1993-07-16 | 1993-08-25 | Pharmaceutical Proteins Ltd | Modified proteins |
| WO1995018224A1 (fr) * | 1993-12-29 | 1995-07-06 | Gene Pharming Europe Bv | Production recombinee de proteines modifiees manquant de certains acides amines |
-
1995
- 1995-07-12 CN CN95194129A patent/CN1157635A/zh active Pending
- 1995-07-12 AU AU28962/95A patent/AU700224B2/en not_active Ceased
- 1995-07-12 EP EP95924467A patent/EP0765390A1/fr not_active Withdrawn
- 1995-07-12 CA CA002193513A patent/CA2193513A1/fr not_active Abandoned
- 1995-07-12 NZ NZ289197A patent/NZ289197A/en unknown
- 1995-07-12 WO PCT/GB1995/001651 patent/WO1996002640A1/fr not_active Application Discontinuation
- 1995-07-12 JP JP8504802A patent/JPH10502816A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JPH10502816A (ja) | 1998-03-17 |
| NZ289197A (en) | 1998-09-24 |
| EP0765390A1 (fr) | 1997-04-02 |
| WO1996002640A1 (fr) | 1996-02-01 |
| AU700224B2 (en) | 1998-12-24 |
| CN1157635A (zh) | 1997-08-20 |
| AU2896295A (en) | 1996-02-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5824837A (en) | Expression of human interleukin-1β in a transgenic animal | |
| CA2093659C (fr) | Sequence de l'adn encodant l'.alpha.-lactalbumine bovine et methode d'utilisation | |
| EP0279582A2 (fr) | Séquences d'ADN pour diriger des protéines vers les glandes mammaires afin d'être sécrétées efficacement | |
| JP2000501602A (ja) | トランスジェニック動物のミルク中に生成されるリソソーム性蛋白質 | |
| WO1999066054A2 (fr) | Fusion analogue d'erythropoietine-albumine serique humaine | |
| CA2092823A1 (fr) | Animaux transgeniques ayant un gene precurseur amyloide de la maladie d'alzheimer | |
| AU669484B2 (en) | Transgenic protein production | |
| JPH08504562A (ja) | ウシ種による組み換えポリペプチドの製造及びトランスジェニック法 | |
| US6210736B1 (en) | Transgenically produced prolactin | |
| Swanson et al. | High level expression of human apolipoprotein AI in transgenic rats raises total serum high density lipoprotein cholesterol and lowers rat apolipoprotein AI | |
| Mikkelsen et al. | Tissue-specific expression in the salivary glands of transgenic mice | |
| CA2193513A1 (fr) | Structures geniques d'alpha-lactalbumine | |
| US6252131B1 (en) | Transgenic mammal having 5-HT3 transgene overexpression in the CMS | |
| CA2373507A1 (fr) | Gene du type prp | |
| US5852224A (en) | α-lactalbumin gene constructs | |
| AU712016B2 (en) | Ikaros transgenic cells and animals | |
| CA2325871A1 (fr) | Lipase humaine stimulee par le sel biliaire, produite a partir de moutons transgeniques | |
| US6191342B1 (en) | Transgenic mice expressing the HIK-ras 4B chimeric gene | |
| JPH05115283A (ja) | プロテインホスフアターゼ阻害物質−１の遺伝子及びその発現 | |
| JP4565531B2 (ja) | ビクニン遺伝子のターゲッティング用ｄｎａ | |
| AU752590B2 (en) | H2-O modified transgenic animals | |
| WO1998058051A1 (fr) | Prolactine produite par voie transgenique |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |