WO1998033887B1 - Growth differentiation factor-8 - Google Patents
Growth differentiation factor-8Info
- Publication number
- WO1998033887B1 WO1998033887B1 PCT/US1998/002479 US9802479W WO9833887B1 WO 1998033887 B1 WO1998033887 B1 WO 1998033887B1 US 9802479 W US9802479 W US 9802479W WO 9833887 B1 WO9833887 B1 WO 9833887B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- gdf
- transgene
- animal
- expression
- transgenic
- Prior art date
Links
- 102000004472 Myostatin Human genes 0.000 title claims abstract 30
- 108010056852 Myostatin Proteins 0.000 title claims abstract 30
- 230000000694 effects Effects 0.000 claims abstract 13
- 241000894007 species Species 0.000 claims abstract 10
- 241000271566 Aves Species 0.000 claims abstract 5
- 241000283690 Bos taurus Species 0.000 claims abstract 5
- 230000000692 anti-sense Effects 0.000 claims abstract 4
- 210000003205 Muscles Anatomy 0.000 claims abstract 3
- 238000004519 manufacturing process Methods 0.000 claims abstract 3
- 210000004602 germ cell Anatomy 0.000 claims abstract 2
- 230000014509 gene expression Effects 0.000 claims 15
- 210000001161 Embryo, Mammalian Anatomy 0.000 claims 8
- 229920000023 polynucleotide Polymers 0.000 claims 7
- 239000002157 polynucleotide Substances 0.000 claims 7
- 241000700605 Viruses Species 0.000 claims 4
- 150000001875 compounds Chemical class 0.000 claims 3
- 230000002452 interceptive Effects 0.000 claims 3
- 229920001184 polypeptide Polymers 0.000 claims 3
- 210000001671 Embryonic Stem Cells Anatomy 0.000 claims 2
- 230000001105 regulatory Effects 0.000 claims 2
- 241000287828 Gallus gallus Species 0.000 claims 1
- 241000288147 Meleagris gallopavo Species 0.000 claims 1
- 210000004027 cells Anatomy 0.000 claims 1
- 235000013601 eggs Nutrition 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 102000004169 proteins and genes Human genes 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 claims 1
- 230000000638 stimulation Effects 0.000 claims 1
- 241001430294 unidentified retrovirus Species 0.000 claims 1
- 241001465754 Metazoa Species 0.000 abstract 3
- 102000004965 antibodies Human genes 0.000 abstract 1
- 108090001123 antibodies Proteins 0.000 abstract 1
Abstract
A transgenic non-human animal of the species selected from the group consisting of avian, bovine, ovine and porcine having a transgene which results in disrupting the production of and/or activity of growth differentiation factor-8 (GDF-8) chromosomally integrated into the germ cells of the animal is disclosed. Also disclosed are methods for making such animals, and methods of treating animals, including humans, with antibodies or antisense directed to GDF-8. The animals so treated are characterized by increased muscle tissue.
Claims
89
AMENDED CLAIMS
[received by the International Bureau on 21 July 1998 (21.07.98); original claim 2 amended; new claims 49-65 added; remaining claims unchanged (4 pages)]
1. A transgenic non-human animal having a transgene disrupting or interfering with expression of growth differentiation factor-8 (GDF-8) chromosomally integrated into the germ cells ofthe animal.
2. The transgenic animal of claim 1 , wherein the animal is selected irom the group of species consisting of murine, avian, bovine, ovine, piscine, murine, and porcine.
3. The transgenic animal of claim 1 where the species is avian.
4. The transgenic animal of claim 1 where the species is bovine.
5. The transgenic animal of claim 1 where the species is porcine.
6. The transgenic animal of claim 1 where the species is ovine.
7. The Txansgcnic animal of claim 1 where the species is piscine.
8. The transgenic ariimal of claim 1 , wherein the transgene comprises GDF-8 antisense polynucleotidc(s).
9. The transgenic animal of claim 1 , wherein the transgene comprises a gene e- ncoding a dominant negative GDF-8 polypeptide,
10. The transgenic animal of claim 1 , wherein the animal is homozygous or heterozygous for GDF-8 polynucleotide.
11. A chicken or turkey egg produced by the transgenic animal of claim 3.
90
44. A method for identifying a compound that affects GDF-8 activity or gene expression comprising: a) incubating the compound with GDF-8 polypeptide, or with a recombinant cell expressing GDF-8 under conditions sufficient to allow the components to interact; and b) deterπώiing the effect ofthe compound on GDF-8 activity or expression.
45. The method of claim 44, wherein tlie effect is inhibition of GDF-8 activity or expression.
46. The method of claim 44, wherein the effect is stimulation of GDF-8 activity or expression.
47. An isolated polynucleotide encoding a truncated GDF-8 polypeptide wherein the truncation is a loss ofthe C-terminai active fragment of GDF-8.
48. The isolated polynucleotide of claim 47, wherein the polynucleotide is as shown in FIGURE 12a.
49. The transgenic animal of claim 1 where the species is murine.
50. A method for producing a transgenic non-human animal having a phenotype characterized by expression of a transgene otherwise not naturally occurring, wherein expression ofthe transgene disrupts or interferes with growth differentiation factor-8 (GDF-8) activity, comprising: a) introducing a transgene in operable linkage with at least one expression regulatory sequence into a zygote of an animal; b) transplanting th e zygote of a) into a pseudopregnant animal; c) allowing the zygote to develope to term; and d) identifying at least one transgenic offspring from c) where expression ofthe transgene disrupts or interferes with GDF-8 activity.
91
51. The method of claim 50, wherein the introduction ofthe transgene into the embryo is by introducing an embryonic stem cell containing the transgene into the embryo.
52. The method of claim 50, wherein the introduction ofthe transgene into the embryo is by infecting the embryo with a virus containing the transgene.
52. The method of claim 52, wherein the virus is a retrovirus.
53. The method of claim 50, wherein the transgene encodes GDF-8 antisense polynucleotide(s).
54. The method of claim 50, wherein the transgene encodes a dominant negative protein that disrupts or interferes with GDF-8 activity.
55. The method of claim 50, wherein the transgenic animal is homozygous or heterozygous for GDF-8 polynucleotide.
56. The method of claim 50, wherein disrupting or interfering with GDF-8 activity in the transgenic non-human animal produces increased muscle mass as compared to a non-transgenic animal ofthe same species.
57. The method of claim 50, wherein the animal is selected from the group consisting of murine, avian, bovine, ovine, piscine, and porcine.
92
58. A method for producing a transgenic non-human animal having a phenot pe characterized by expression of a transgene otherwise not naturally occurring, wherein expression ofthe transgene disrupts or interferes with expression of growth differentiation factor-8 (GDF-8), comprising: a) introducing a transgene in operable linkage with at least one expression regulatory sequence into a zygote of an animal; b) transplanting the zygote of a) into a pseudopregnant animal ; c) allowing the zygote to develope to term; and d) identifying at least one transgenic offspring from c) where expression ofthe transgene disrupts or interferes with expression of GDF-8.
59. The method of claim 58, wherein the introduction of tlie transgene into the embryo is by introducing an embryonic stem cell containing the transgene into the embryo.
60. The method of claim 58, wherein the introduction ofthe transgene into the embryo is by infecting the embryo with a virus containing the transgene.
61. The method of claim 60, wherein the virus is a rctrovirus.
62. The method of claim 58, wherein the transgene encodes GDF-8 antisense polynucleotidets).
63. The method of claim 58, wherein the transgenic animal is homozygous or heterozygous for GDF-8 polynucleotide.
64. The method of claim 58, wherein disrupting or interfering with GDF-8 activity in tlie transgenic non-human animal produces increased muscle mass as compared to a non-transgenic animal ofthe same species.
65. The method of claim 58, wherein the animal is selected from the group consisting of murine, avian, bovine, ovine, piscine, and porcine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU62742/98A AU6274298A (en) | 1997-02-05 | 1998-02-05 | Growth differentiation factor-8 |
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/795,071 US5994618A (en) | 1997-02-05 | 1997-02-05 | Growth differentiation factor-8 transgenic mice |
| US08/795,071 | 1997-02-05 | ||
| US84791097A | 1997-04-28 | 1997-04-28 | |
| US08/847,910 | 1997-04-28 | ||
| US86244597A | 1997-05-23 | 1997-05-23 | |
| US08/862,445 | 1997-05-23 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO1998033887A1 WO1998033887A1 (en) | 1998-08-06 |
| WO1998033887B1 true WO1998033887B1 (en) | 1998-09-11 |
Family
ID=27419913
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1998/002479 WO1998033887A1 (en) | 1997-02-05 | 1998-02-05 | Growth differentiation factor-8 |
Country Status (3)
| Country | Link |
|---|---|
| US (1) | US20080311584A1 (en) |
| AU (1) | AU6274298A (en) |
| WO (1) | WO1998033887A1 (en) |
Families Citing this family (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1333035A3 (en) | 1993-03-19 | 2004-07-07 | The Johns Hopkins University School Of Medicine | Growth differentiation factor-8 |
| US7566768B1 (en) | 1995-10-26 | 2009-07-28 | The Johns Hopkins University School Of Medicine | Promyostatin peptides and methods of using same |
| US6465239B1 (en) * | 1993-03-19 | 2002-10-15 | The John Hopkins University School Of Medicine | Growth differentiation factor-8 nucleic acid and polypeptides from aquatic species and non-human transgenic aquatic species |
| US7393682B1 (en) | 1993-03-19 | 2008-07-01 | The Johns Hopkins University School Of Medicine | Polynucleotides encoding promyostatin polypeptides |
| US6607884B1 (en) | 1993-03-19 | 2003-08-19 | The Johns Hopkins University School Of Medicine | Methods of detecting growth differentiation factor-8 |
| US5994618A (en) | 1997-02-05 | 1999-11-30 | Johns Hopkins University School Of Medicine | Growth differentiation factor-8 transgenic mice |
| US7332575B2 (en) | 1994-03-18 | 2008-02-19 | The Johns Hopkins University School Of Medicine | Growth differentiation factor-8 nucleic acid and polypeptide from aquatic species, and transgenic aquatic species |
| US6008434A (en) | 1994-07-08 | 1999-12-28 | Johns Hopkins University School Of Medicine | Growth differentiation factor-11 transgenic mice |
| AU756620B2 (en) * | 1997-07-14 | 2003-01-16 | University Of Liege | Mutations in the myostation gene cause double-muscling in mammals |
| US6103466A (en) * | 1997-07-14 | 2000-08-15 | University Of Liege | Double-muscling in mammals |
| US6696260B1 (en) | 1997-08-01 | 2004-02-24 | The Johns Hopkins University School Of Medicine | Methods to identify growth differentiation factor (GDF) binding proteins |
| US6891082B2 (en) | 1997-08-01 | 2005-05-10 | The Johns Hopkins University School Of Medicine | Transgenic non-human animals expressing a truncated activintype II receptor |
| US6656475B1 (en) * | 1997-08-01 | 2003-12-02 | The Johns Hopkins University School Of Medicine | Growth differentiation factor receptors, agonists and antagonists thereof, and methods of using same |
| GB2333706A (en) * | 1998-02-02 | 1999-08-04 | Merck & Co Inc | Method for increasing muscle mass in animals |
| CA2319703C (en) * | 1998-02-05 | 2005-09-20 | The Johns Hopkins University School Of Medicine | Growth differentiation factor-8 |
| US6369201B1 (en) | 1998-02-19 | 2002-04-09 | Metamorphix International, Inc. | Myostatin multimers |
| EP1075272B1 (en) * | 1998-05-06 | 2009-07-15 | Metamorphix, Inc. | Methods for treating diabetes by inhibiting gdf-8 |
| GB2346146A (en) * | 1998-08-14 | 2000-08-02 | Univ Texas | Calcineurin-dependent control of skeletal muscle fiber type |
| NZ513642A (en) * | 1999-01-21 | 2004-02-27 | Metamorphix Inc | Growth differentiation factor inhibitors and uses therefor |
| US6284882B1 (en) * | 1999-06-10 | 2001-09-04 | Abbott Laboratories | Myostatin gene promoter and inhibition of activation thereof |
| ZA200003786B (en) | 1999-07-30 | 2002-01-21 | Pfizer Prod Inc | Myostatin regulatory region, nucleotide sequence determination and methods for its use. |
| WO2001053350A1 (en) | 2000-01-18 | 2001-07-26 | Agresearch Limited | Myostatin and mimetics thereof |
| WO2002014492A2 (en) * | 2000-08-14 | 2002-02-21 | Iogenetics, Llc | Fatty liver disease resistant bovines |
| US7037501B2 (en) | 2001-01-04 | 2006-05-02 | Regents Of The University Of Minnesota | Myostatin immnoconjugate |
| TWI329129B (en) | 2001-02-08 | 2010-08-21 | Wyeth Corp | Modified and stabilized gdf propeptides and uses thereof |
| AU2012204098B2 (en) * | 2001-04-24 | 2014-05-15 | The Johns Hopkins University | Use of follistatin to increase muscle mass |
| US7320789B2 (en) | 2001-09-26 | 2008-01-22 | Wyeth | Antibody inhibitors of GDF-8 and uses thereof |
| WO2003072714A2 (en) | 2002-02-21 | 2003-09-04 | Wyeth | Follistatin domain containing proteins |
| JP4429729B2 (en) | 2002-02-21 | 2010-03-10 | ワイス エルエルシー | GASP1; follistatin domain-containing protein |
| US7261893B2 (en) | 2002-10-22 | 2007-08-28 | Wyeth | Neutralizing antibodies against GDF-8 and uses therefor |
| EP1635870A2 (en) | 2003-06-02 | 2006-03-22 | Wyeth | Use of myostatin (gdf8) inhibitors in conjunction with corticosteroids for treating neuromuscular disorders |
| EP1699820A2 (en) | 2003-12-31 | 2006-09-13 | Schering-Plough Ltd. | Neutralizing epitope-based growth enhancing vaccine |
| US20080118487A1 (en) | 2004-09-30 | 2008-05-22 | Orico Limited | Myostatin Isoform |
| EP1831372A2 (en) | 2004-12-30 | 2007-09-12 | Schering-Plough Ltd. | Neutralizing epitope-based growth enhancing vaccine |
| NZ538097A (en) * | 2005-02-07 | 2006-07-28 | Ovita Ltd | Method and compositions for improving wound healing |
| CN103450359B (en) | 2005-08-19 | 2018-07-24 | 惠氏有限责任公司 | The antagonist antibodies of anti-GDF-8 and the purposes in ALS and other GDF-8- associated disorder treatments |
| GB2433320B (en) * | 2005-12-16 | 2009-10-07 | Norwegian University Of Life S | Diagnostic method |
| EP1798292A1 (en) * | 2005-12-19 | 2007-06-20 | Nutreco Nederland B.V. | Methods for improving turkey meat production |
| CN100450545C (en) * | 2006-08-03 | 2009-01-14 | 中国医学科学院基础医学研究所 | Application of musculus growth inhibin for preparing anticarcinogen |
| AU2007279456A1 (en) * | 2006-08-03 | 2008-02-07 | Myostin Therapeutics Pty Ltd | Myostatin antagonists |
| CN102653764B (en) * | 2012-04-26 | 2014-03-19 | 天津农学院 | Method for introducing frame-shift mutation in MSTN (myostatin) genes of cattle |
| EP2861617A1 (en) | 2012-06-15 | 2015-04-22 | Pfizer Inc. | Improved antagonist antibodies against gdf-8 and uses therefor |
| CN104768969B (en) | 2012-09-13 | 2021-04-16 | 百时美施贵宝公司 | Fibronectin based scaffold domain proteins that bind to myostatin |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5585479A (en) * | 1992-07-24 | 1996-12-17 | The United States Of America As Represented By The Secretary Of The Navy | Antisense oligonucleotides directed against human ELAM-I RNA |
| US5716806A (en) * | 1995-06-05 | 1998-02-10 | Human Genome Sciences, Inc. | Human inositiol monophosphatase H1 polynucleotides |
| US5756295A (en) * | 1994-12-05 | 1998-05-26 | Takeda Chemical Industries, Ltd. | DNA primer and a method for screening DNAS |
| CN1151269C (en) * | 1995-06-06 | 2004-05-26 | 扬·维吉 | Method of and apparatus for diagnostic DNA testing |
| US6103466A (en) * | 1997-07-14 | 2000-08-15 | University Of Liege | Double-muscling in mammals |
-
1998
- 1998-02-05 AU AU62742/98A patent/AU6274298A/en not_active Abandoned
- 1998-02-05 WO PCT/US1998/002479 patent/WO1998033887A1/en active Application Filing
-
2008
- 2008-05-30 US US12/130,771 patent/US20080311584A1/en not_active Abandoned
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