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Growth differentiation factor 9
Identifiers
Symbols GDF9;
External IDs OMIM601918 MGI95692 HomoloGene3851 GeneCards: GDF9 Gene
RNA expression pattern
PBB GE GDF9 221314 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 2661 14566
Ensembl ENSG00000164404 ENSMUSG00000018238
UniProt O60383 Q3UWR9
RefSeq (mRNA) NM_005260 NM_008110
RefSeq (protein) NP_005251 NP_032136
Location (UCSC) Chr 5:
132.22 - 132.23 Mb
Chr 11:
53.28 - 53.28 Mb
PubMed search [1] [2]

Growth/differentiation factor 9 is a protein that in humans is encoded by the GDF9 gene.[1][2]

Growth factors synthesized by ovarian somatic cells directly affect oocyte growth and function. Growth differentiation factor-9 (GDF9) is expressed in oocytes and is thought to be required for ovarian folliculogenesis. GDF9 is a member of the transforming growth factor-beta (TGFβ) superfamily.[2]

GDF9 plays an important role in the development of primary follicles in the ovary.[3] It has a critical role in granulosa cell and theca cell growth, as well as in differentiation and maturation of the oocyte.[4][5]

GDF9 has been connected to differences in ovulation rate[6][7] and in premature cessation of ovary function,[8] therefore has a significant role in fertility.

The cell surface receptor through which GDF9 generates a signal is the bone morphogenetic protein type II receptor (BMPR2).[9][10]

References

  1. ^ McGrath SA, Esquela AF, Lee SJ (Jun 1995). "Oocyte-specific expression of growth/differentiation factor-9". Mol Endocrinol 9 (1): 131-6. PMID 7760846.  
  2. ^ a b "Entrez Gene: GDF9 growth differentiation factor 9". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2661.  
  3. ^ Juengel J, Bodensteiner K, Heath D, Hudson N, Moeller C, Smith P, Galloway S, Davis G, Sawyer H, McNatty K (2004). "Physiology of GDF9 and BMP15 signalling molecules". Anim Reprod Sci 82-83: 447–60. doi:10.1016/j.anireprosci.2004.04.021. PMID 15271472.  
  4. ^ Hreinsson J, Scott J, Rasmussen C, Swahn M, Hsueh A, Hovatta O (2002). "Growth differentiation factor-9 promotes the growth, development, and survival of human ovarian follicles in organ culture". J Clin Endocrinol Metab 87 (1): 316–21. doi:10.1210/jc.87.1.316. PMID 11788667.   link
  5. ^ Su Y, Wu X, O'Brien M, Pendola F, Denegre J, Matzuk M, Eppig J (2004). "Synergistic roles of BMP15 and GDF9 in the development and function of the oocyte-cumulus cell complex in mice: genetic evidence for an oocyte-granulosa cell regulatory loop". Dev Biol 276 (1): 64–73. doi:10.1016/j.ydbio.2004.08.020. PMID 15531364.  
  6. ^ McNatty K, Hudson N, Whiting L, Reader K, Lun S, Western A, Heath D, Smith P, Moore L, Juengel J. "The Effects of Immunizing Sheep with Different BMP15 or GDF9 Peptide Sequences on Ovarian Follicular Activity and Ovulation Rate". Biol Reprod. PMID 17093201.  
  7. ^ Juengel J, Hudson N, Whiting L, McNatty K (2004). "Effects of immunization against bone morphogenetic protein 15 and growth differentiation factor 9 on ovulation rate, fertilization, and pregnancy in ewes". Biol Reprod 70 (3): 557–61. doi:10.1095/biolreprod.103.023333. PMID 14585806.  
  8. ^ Kovanci E, Rohozinski J, Simpson J, Heard M, Bishop C, Carson S (2007). "Growth differentiating factor-9 mutations may be associated with premature ovarian failure". Fertil Steril 87 (1): 143–6. doi:10.1016/j.fertnstert.2006.05.079. PMID 17156781.  
  9. ^ Mazerbourg S, Hsueh A (2006). "Genomic analyses facilitate identification of receptors and signalling pathways for growth differentiation factor 9 and related orphan bone morphogenetic protein/growth differentiation factor ligands". Hum Reprod Update 12 (4): 373–83. doi:10.1093/humupd/dml014. PMID 16603567.  
  10. ^ Vitt U, Mazerbourg S, Klein C, Hsueh A (2002). "Bone morphogenetic protein receptor type II is a receptor for growth differentiation factor-9". Biol Reprod 67 (2): 473–80. doi:10.1095/biolreprod67.2.473. PMID 12135884.  

Further reading

  • McPherron AC, Lee SJ (1993). "GDF-3 and GDF-9: two new members of the transforming growth factor-beta superfamily containing a novel pattern of cysteines.". J. Biol. Chem. 268 (5): 3444–9. PMID 8429021.  
  • Dong J, Albertini DF, Nishimori K, et al. (1996). "Growth differentiation factor-9 is required during early ovarian folliculogenesis.". Nature 383 (6600): 531–5. doi:10.1038/383531a0. PMID 8849725.  
  • Aaltonen J, Laitinen MP, Vuojolainen K, et al. (1999). "Human growth differentiation factor 9 (GDF-9) and its novel homolog GDF-9B are expressed in oocytes during early folliculogenesis.". J. Clin. Endocrinol. Metab. 84 (8): 2744–50. doi:10.1210/jc.84.8.2744. PMID 10443672.  
  • Gilboa L, Nohe A, Geissendörfer T, et al. (2000). "Bone morphogenetic protein receptor complexes on the surface of live cells: a new oligomerization mode for serine/threonine kinase receptors.". Mol. Biol. Cell 11 (3): 1023–35. PMID 10712517.  
  • Vitt UA, Mazerbourg S, Klein C, Hsueh AJ (2003). "Bone morphogenetic protein receptor type II is a receptor for growth differentiation factor-9.". Biol. Reprod. 67 (2): 473–80. doi:10.1095/biolreprod67.2.473. PMID 12135884.  
  • Liao WX, Moore RK, Otsuka F, Shimasaki S (2003). "Effect of intracellular interactions on the processing and secretion of bone morphogenetic protein-15 (BMP-15) and growth and differentiation factor-9. Implication of the aberrant ovarian phenotype of BMP-15 mutant sheep.". J. Biol. Chem. 278 (6): 3713–9. doi:10.1074/jbc.M210598200. PMID 12446716.  
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMID 12477932.  
  • Liao WX, Moore RK, Shimasaki S (2004). "Functional and molecular characterization of naturally occurring mutations in the oocyte-secreted factors bone morphogenetic protein-15 and growth and differentiation factor-9.". J. Biol. Chem. 279 (17): 17391–6. doi:10.1074/jbc.M401050200. PMID 14970198.  
  • Schmutz J, Martin J, Terry A, et al. (2004). "The DNA sequence and comparative analysis of human chromosome 5.". Nature 431 (7006): 268–74. doi:10.1038/nature02919. PMID 15372022.  
  • Goehler H, Lalowski M, Stelzl U, et al. (2004). "A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington's disease.". Mol. Cell 15 (6): 853–65. doi:10.1016/j.molcel.2004.09.016. PMID 15383276.  
  • Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMID 15489334.  
  • Stelzl U, Worm U, Lalowski M, et al. (2005). "A human protein-protein interaction network: a resource for annotating the proteome.". Cell 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. PMID 16169070.  
  • Dixit H, Rao LK, Padmalatha V, et al. (2007). "Mutational screening of the coding region of growth differentiation factor 9 gene in Indian women with ovarian failure.". Menopause (New York, N.Y.) 12 (6): 749–54. doi:10.1097/01.gme.0000184424.96437.7a. PMID 16278619.  
  • Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMID 16344560.  
  • Laissue P, Christin-Maitre S, Touraine P, et al. (2006). "Mutations and sequence variants in GDF9 and BMP15 in patients with premature ovarian failure.". Eur. J. Endocrinol. 154 (5): 739–44. doi:10.1530/eje.1.02135. PMID 16645022.  
  • Palmer JS, Zhao ZZ, Hoekstra C, et al. (2007). "Novel variants in growth differentiation factor 9 in mothers of dizygotic twins.". J. Clin. Endocrinol. Metab. 91 (11): 4713–6. doi:10.1210/jc.2006-0970. PMID 16954162.  
  • Chand AL, Ponnampalam AP, Harris SE, et al. (2006). "Mutational analysis of BMP15 and GDF9 as candidate genes for premature ovarian failure.". Fertil. Steril. 86 (4): 1009–12. doi:10.1016/j.fertnstert.2006.02.107. PMID 17027369.  
  • Kovanci E, Rohozinski J, Simpson JL, et al. (2007). "Growth differentiating factor-9 mutations may be associated with premature ovarian failure.". Fertil. Steril. 87 (1): 143–6. doi:10.1016/j.fertnstert.2006.05.079. PMID 17156781.  
  • Hanavadi S, Martin TA, Watkins G, et al. (2007). "The role of growth differentiation factor-9 (GDF-9) and its analog, GDF-9b/BMP-15, in human breast cancer.". Ann. Surg. Oncol. 14 (7): 2159–66. doi:10.1245/s10434-007-9397-5. PMID 17453295.  

External links

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edit
Growth differentiation factor 9
Identifiers
SymbolsGDF9;
External IDsOMIM601918 MGI95692 HomoloGene3851 GeneCards: GDF9 Gene
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez266114566
EnsemblENSG00000164404ENSMUSG00000018238
UniProtO60383Q3UWR9
RefSeq (mRNA)NM_005260NM_008110
RefSeq (protein)NP_005251NP_032136
Location (UCSC)Chr 5:
132.22 - 132.23 Mb
Chr 11:
53.28 - 53.28 Mb
PubMed search[1][2]

Growth/differentiation factor 9 is a protein that in humans is encoded by the GDF9 gene.[1][2]

Growth factors synthesized by ovarian somatic cells directly affect oocyte growth and function. Growth differentiation factor-9 (GDF9) is expressed in oocytes and is thought to be required for ovarian folliculogenesis. GDF9 is a member of the transforming growth factor-beta (TGFβ) superfamily.[2]

GDF9 plays an important role in the development of primary follicles in the ovary.[3] It has a critical role in granulosa cell and theca cell growth, as well as in differentiation and maturation of the oocyte.[4][5]

GDF9 has been connected to differences in ovulation rate[6][7] and in premature cessation of ovary function,[8] therefore has a significant role in fertility.

The cell surface receptor through which GDF9 generates a signal is the bone morphogenetic protein type II receptor (BMPR2).[9][10]

References

  1. ^ McGrath SA, Esquela AF, Lee SJ (Jun 1995). [Expression error: Unexpected < operator "Oocyte-specific expression of growth/differentiation factor-9"]. Mol Endocrinol 9 (1): 131–6. doi:10.1210/me.9.1.131. PMID 7760846. 
  2. ^ a b "Entrez Gene: GDF9 growth differentiation factor 9". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2661. 
  3. ^ Juengel J, Bodensteiner K, Heath D, Hudson N, Moeller C, Smith P, Galloway S, Davis G, Sawyer H, McNatty K (2004). [Expression error: Unexpected < operator "Physiology of GDF9 and BMP15 signalling molecules"]. Anim Reprod Sci 82-83: 447–60. doi:10.1016/j.anireprosci.2004.04.021. PMID 15271472. 
  4. ^ Hreinsson J, Scott J, Rasmussen C, Swahn M, Hsueh A, Hovatta O (2002). [Expression error: Unexpected < operator "Growth differentiation factor-9 promotes the growth, development, and survival of human ovarian follicles in organ culture"]. J Clin Endocrinol Metab 87 (1): 316–21. doi:10.1210/jc.87.1.316. PMID 11788667.  link
  5. ^ Su Y, Wu X, O'Brien M, Pendola F, Denegre J, Matzuk M, Eppig J (2004). [Expression error: Unexpected < operator "Synergistic roles of BMP15 and GDF9 in the development and function of the oocyte-cumulus cell complex in mice: genetic evidence for an oocyte-granulosa cell regulatory loop"]. Dev Biol 276 (1): 64–73. doi:10.1016/j.ydbio.2004.08.020. PMID 15531364. 
  6. ^ McNatty K, Hudson N, Whiting L, Reader K, Lun S, Western A, Heath D, Smith P, Moore L, Juengel J (2007). [Expression error: Unexpected < operator "The Effects of Immunizing Sheep with Different BMP15 or GDF9 Peptide Sequences on Ovarian Follicular Activity and Ovulation Rate"]. Biol Reprod 76 (4): 552–60. doi:10.1095/biolreprod.106.054361. PMID 17093201. 
  7. ^ Juengel J, Hudson N, Whiting L, McNatty K (2004). [Expression error: Unexpected < operator "Effects of immunization against bone morphogenetic protein 15 and growth differentiation factor 9 on ovulation rate, fertilization, and pregnancy in ewes"]. Biol Reprod 70 (3): 557–61. doi:10.1095/biolreprod.103.023333. PMID 14585806. 
  8. ^ Kovanci E, Rohozinski J, Simpson J, Heard M, Bishop C, Carson S (2007). [Expression error: Unexpected < operator "Growth differentiating factor-9 mutations may be associated with premature ovarian failure"]. Fertil Steril 87 (1): 143–6. doi:10.1016/j.fertnstert.2006.05.079. PMID 17156781. 
  9. ^ Mazerbourg S, Hsueh A (2006). [Expression error: Unexpected < operator "Genomic analyses facilitate identification of receptors and signalling pathways for growth differentiation factor 9 and related orphan bone morphogenetic protein/growth differentiation factor ligands"]. Hum Reprod Update 12 (4): 373–83. doi:10.1093/humupd/dml014. PMID 16603567. 
  10. ^ Vitt U, Mazerbourg S, Klein C, Hsueh A (2002). [Expression error: Unexpected < operator "Bone morphogenetic protein receptor type II is a receptor for growth differentiation factor-9"]. Biol Reprod 67 (2): 473–80. doi:10.1095/biolreprod67.2.473. PMID 12135884. 

Further reading

  • McPherron AC, Lee SJ (1993). [Expression error: Unexpected < operator "GDF-3 and GDF-9: two new members of the transforming growth factor-beta superfamily containing a novel pattern of cysteines."]. J. Biol. Chem. 268 (5): 3444–9. PMID 8429021. 
  • Dong J, Albertini DF, Nishimori K, et al. (1996). [Expression error: Unexpected < operator "Growth differentiation factor-9 is required during early ovarian folliculogenesis."]. Nature 383 (6600): 531–5. doi:10.1038/383531a0. PMID 8849725. 
  • Aaltonen J, Laitinen MP, Vuojolainen K, et al. (1999). [Expression error: Unexpected < operator "Human growth differentiation factor 9 (GDF-9) and its novel homolog GDF-9B are expressed in oocytes during early folliculogenesis."]. J. Clin. Endocrinol. Metab. 84 (8): 2744–50. doi:10.1210/jc.84.8.2744. PMID 10443672. 
  • Gilboa L, Nohe A, Geissendörfer T, et al. (2000). [Expression error: Unexpected < operator "Bone morphogenetic protein receptor complexes on the surface of live cells: a new oligomerization mode for serine/threonine kinase receptors."]. Mol. Biol. Cell 11 (3): 1023–35. PMID 10712517. 
  • Vitt UA, Mazerbourg S, Klein C, Hsueh AJ (2003). [Expression error: Unexpected < operator "Bone morphogenetic protein receptor type II is a receptor for growth differentiation factor-9."]. Biol. Reprod. 67 (2): 473–80. doi:10.1095/biolreprod67.2.473. PMID 12135884. 
  • Liao WX, Moore RK, Otsuka F, Shimasaki S (2003). [Expression error: Unexpected < operator "Effect of intracellular interactions on the processing and secretion of bone morphogenetic protein-15 (BMP-15) and growth and differentiation factor-9. Implication of the aberrant ovarian phenotype of BMP-15 mutant sheep."]. J. Biol. Chem. 278 (6): 3713–9. doi:10.1074/jbc.M210598200. PMID 12446716. 
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). [Expression error: Unexpected < operator "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences."]. Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMID 12477932. 
  • Liao WX, Moore RK, Shimasaki S (2004). [Expression error: Unexpected < operator "Functional and molecular characterization of naturally occurring mutations in the oocyte-secreted factors bone morphogenetic protein-15 and growth and differentiation factor-9."]. J. Biol. Chem. 279 (17): 17391–6. doi:10.1074/jbc.M401050200. PMID 14970198. 
  • Schmutz J, Martin J, Terry A, et al. (2004). [Expression error: Unexpected < operator "The DNA sequence and comparative analysis of human chromosome 5."]. Nature 431 (7006): 268–74. doi:10.1038/nature02919. PMID 15372022. 
  • Goehler H, Lalowski M, Stelzl U, et al. (2004). [Expression error: Unexpected < operator "A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington's disease."]. Mol. Cell 15 (6): 853–65. doi:10.1016/j.molcel.2004.09.016. PMID 15383276. 
  • Gerhard DS, Wagner L, Feingold EA, et al. (2004). [Expression error: Unexpected < operator "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."]. Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMID 15489334. 
  • Stelzl U, Worm U, Lalowski M, et al. (2005). [Expression error: Unexpected < operator "A human protein-protein interaction network: a resource for annotating the proteome."]. Cell 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. PMID 16169070. 
  • Dixit H, Rao LK, Padmalatha V, et al. (2007). [Expression error: Unexpected < operator "Mutational screening of the coding region of growth differentiation factor 9 gene in Indian women with ovarian failure."]. Menopause (New York, N.Y.) 12 (6): 749–54. doi:10.1097/01.gme.0000184424.96437.7a. PMID 16278619. 
  • Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). [Expression error: Unexpected < operator "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes."]. Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMID 16344560. 
  • Laissue P, Christin-Maitre S, Touraine P, et al. (2006). [Expression error: Unexpected < operator "Mutations and sequence variants in GDF9 and BMP15 in patients with premature ovarian failure."]. Eur. J. Endocrinol. 154 (5): 739–44. doi:10.1530/eje.1.02135. PMID 16645022. 
  • Palmer JS, Zhao ZZ, Hoekstra C, et al. (2007). [Expression error: Unexpected < operator "Novel variants in growth differentiation factor 9 in mothers of dizygotic twins."]. J. Clin. Endocrinol. Metab. 91 (11): 4713–6. doi:10.1210/jc.2006-0970. PMID 16954162. 
  • Chand AL, Ponnampalam AP, Harris SE, et al. (2006). [Expression error: Unexpected < operator "Mutational analysis of BMP15 and GDF9 as candidate genes for premature ovarian failure."]. Fertil. Steril. 86 (4): 1009–12. doi:10.1016/j.fertnstert.2006.02.107. PMID 17027369. 
  • Kovanci E, Rohozinski J, Simpson JL, et al. (2007). [Expression error: Unexpected < operator "Growth differentiating factor-9 mutations may be associated with premature ovarian failure."]. Fertil. Steril. 87 (1): 143–6. doi:10.1016/j.fertnstert.2006.05.079. PMID 17156781. 
  • Hanavadi S, Martin TA, Watkins G, et al. (2007). [Expression error: Unexpected < operator "The role of growth differentiation factor-9 (GDF-9) and its analog, GDF-9b/BMP-15, in human breast cancer."]. Ann. Surg. Oncol. 14 (7): 2159–66. doi:10.1245/s10434-007-9397-5. PMID 17453295. 

External links


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