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Department of Tissue Growth and Repair (J.L.D., A.J.C.)
Genetics Institute, Inc. Cambridge, Massachusetts 02140
Departments of Orthopaedic Surgery and Biological Chemistry
(K.M.L.) University of California Los Angeles School of
Medicine Los Angeles, California 90095
Departments of
Pathology (P.W., J.E., M.M.M.), Cell Biology (M.M.M.), and Molecular
and Human Genetics (J.E., M.M.M.) Baylor College of Medicine
Houston, Texas 77030
We have taken advantage of the sequence relationships among the bone morphogenetic proteins (BMPs) to identify the mouse Bmp15 and human BMP15 genes. The 392-amino acid prepropeptides encoded by these BMP genes exhibit significant homology to each other, although the 70% identity observed between the 125-amino acid mature peptides is considerably lower than that seen in comparisons of other mouse and human orthologs. Both genes share a common structural organization and encode mature peptides that lack the cysteine residue normally involved in the formation of a covalent dimer. In addition, mouse Bmp15 and human BMP15 map to conserved syntenic regions on the X chromosome. We demonstrate, through a combination of Northern blot and in situ hybridization analyses, that mouse Bmp15 is expressed specifically in the oocyte beginning at the one-layer primary follicle stage and continuing through ovulation. Interestingly, BMP-15 is most closely related to and shares a coincident expression pattern with the mouse growth/differentiation factor 9 (GDF-9) gene that is essential for female fertility. Our findings will be important for defining the role of BMP-15 in follicular development.
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K. Bogner, K.-D. Hinsch, P. Nayudu, L. Konrad, C. Cassara, and E. Hinsch Localization and synthesis of zona pellucida proteins in the marmoset monkey (Callithrix jacchus) ovary Mol. Hum. Reprod., July 1, 2004; 10(7): 481 - 488. [Abstract] [Full Text] [PDF] |
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J. P. Hanrahan, S. M. Gregan, P. Mulsant, M. Mullen, G. H. Davis, R. Powell, and S. M. Galloway Mutations in the Genes for Oocyte-Derived Growth Factors GDF9 and BMP15 Are Associated with Both Increased Ovulation Rate and Sterility in Cambridge and Belclare Sheep (Ovis aries) Biol Reprod, April 1, 2004; 70(4): 900 - 909. [Abstract] [Full Text] [PDF] |
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S. Mazerbourg, C. Klein, J. Roh, N. Kaivo-Oja, D. G. Mottershead, O. Korchynskyi, O. Ritvos, and A. J. W. Hsueh Growth Differentiation Factor-9 Signaling Is Mediated by the Type I Receptor, Activin Receptor-Like Kinase 5 Mol. Endocrinol., March 1, 2004; 18(3): 653 - 665. [Abstract] [Full Text] [PDF] |
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S. Shimasaki, R. K. Moore, F. Otsuka, and G. F. Erickson The Bone Morphogenetic Protein System In Mammalian Reproduction Endocr. Rev., February 1, 2004; 25(1): 72 - 101. [Abstract] [Full Text] [PDF] |
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O. M. Onagbesan, V. Bruggeman, P. Van As, K. Tona, J. Williams, and E. Decuypere BMPs and BMPRs in chicken ovary and effects of BMP-4 and -7 on granulosa cell proliferation and progesterone production in vitro Am J Physiol Endocrinol Metab, November 1, 2003; 285(5): E973 - E983. [Abstract] [Full Text] [PDF] |
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E. E. Nilsson and M. K. Skinner Bone Morphogenetic Protein-4 Acts as an Ovarian Follicle Survival Factor and Promotes Primordial Follicle Development Biol Reprod, October 1, 2003; 69(4): 1265 - 1272. [Abstract] [Full Text] [PDF] |
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D. M. Duffy Growth Differentiation Factor-9 Is Expressed by the Primate Follicle Throughout the Periovulatory Interval Biol Reprod, August 1, 2003; 69(2): 725 - 732. [Abstract] [Full Text] [PDF] |
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C. Glister, N. P. Groome, and P. G. Knight Oocyte-Mediated Suppression of Follicle-Stimulating Hormone- and Insulin-Like Growth Factor-Induced Secretion of Steroids and Inhibin-Related Proteins by Bovine Granulosa Cells In Vitro: Possible Role of Transforming Growth Factor {alpha} Biol Reprod, March 1, 2003; 68(3): 758 - 765. [Abstract] [Full Text] [PDF] |
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N. Kaivo-Oja, J. Bondestam, M. Kamarainen, J. Koskimies, U. Vitt, M. Cranfield, K. Vuojolainen, J. P. Kallio, V. M. Olkkonen, M. Hayashi, et al. Growth Differentiation Factor-9 Induces Smad2 Activation and Inhibin B Production in Cultured Human Granulosa-Luteal Cells J. Clin. Endocrinol. Metab., February 1, 2003; 88(2): 755 - 762. [Abstract] [Full Text] [PDF] |
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W. X. Liao, R. K. Moore, F. Otsuka, and S. Shimasaki 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., January 31, 2003; 278(6): 3713 - 3719. [Abstract] [Full Text] [PDF] |
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R. K. Moore, F. Otsuka, and S. Shimasaki Molecular Basis of Bone Morphogenetic Protein-15 Signaling in Granulosa Cells J. Biol. Chem., January 3, 2003; 278(1): 304 - 310. [Abstract] [Full Text] [PDF] |
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J.-S. Roh, J. Bondestam, S. Mazerbourg, N. Kaivo-Oja, N. Groome, O. Ritvos, and A. J. W. Hsueh Growth Differentiation Factor-9 Stimulates Inhibin Production and Activates Smad2 in Cultured Rat Granulosa Cells Endocrinology, January 1, 2003; 144(1): 172 - 178. [Abstract] [Full Text] [PDF] |
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H. Chang, C. W. Brown, and M. M. Matzuk Genetic Analysis of the Mammalian Transforming Growth Factor-{beta} Superfamily Endocr. Rev., December 1, 2002; 23(6): 787 - 823. [Abstract] [Full Text] [PDF] |
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J. Huntriss, R. Gosden, M. Hinkins, B. Oliver, D. Miller, A.J. Rutherford, and H.M. Picton Isolation, characterization and expression of the human Factor In the Germline alpha (FIGLA) gene in ovarian follicles and oocytes Mol. Hum. Reprod., December 1, 2002; 8(12): 1087 - 1095. [Abstract] [Full Text] [PDF] |
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J. L. Juengel, N. L. Hudson, D. A. Heath, P. Smith, K. L. Reader, S. B. Lawrence, A. R. O'Connell, M. P.E. Laitinen, M. Cranfield, N. P. Groome, et al. Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 Are Essential for Ovarian Follicular Development in Sheep Biol Reprod, December 1, 2002; 67(6): 1777 - 1789. [Abstract] [Full Text] [PDF] |
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A. Narula, S. Kilen, E. Ma, J. Kroeger, E. Goldberg, and T. K. Woodruff Smad4 Overexpression Causes Germ Cell Ablation and Leydig Cell Hyperplasia in Transgenic Mice Am. J. Pathol., November 1, 2002; 161(5): 1723 - 1734. [Abstract] [Full Text] [PDF] |
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E. E. Nilsson and M. K. Skinner Growth and Differentiation Factor-9 Stimulates Progression of Early Primary but Not Primordial Rat Ovarian Follicle Development Biol Reprod, September 1, 2002; 67(3): 1018 - 1024. [Abstract] [Full Text] [PDF] |
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U. A. Vitt, S. Mazerbourg, C. Klein, and A. J.W. Hsueh Bone Morphogenetic Protein Receptor Type II Is a Receptor for Growth Differentiation Factor-9 Biol Reprod, August 1, 2002; 67(2): 473 - 480. [Abstract] [Full Text] [PDF] |
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C. P. Leo, S. Y. Hsu, and A. J. W. Hsueh Hormonal Genomics Endocr. Rev., June 1, 2002; 23(3): 369 - 381. [Abstract] [Full Text] [PDF] |
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N. Yamamoto, L. K. Christenson, J. M. MCAllister, and J. F. Strauss III Growth Differentiation Factor-9 Inhibits 3'5'-Adenosine Monophosphate-Stimulated Steroidogenesis in Human Granulosa and Theca Cells J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2849 - 2856. [Abstract] [Full Text] [PDF] |
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D. Tomic, S.G. Brodie, C. Deng, R.J. Hickey, J.K. Babus, L.H. Malkas, and J.A. Flaws Smad 3 May Regulate Follicular Growth in the Mouse Ovary Biol Reprod, April 1, 2002; 66(4): 917 - 923. [Abstract] [Full Text] [PDF] |
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R. Jaatinen, J. Bondestam, T. Raivio, K. Hilden, L. Dunkel, N. Groome, and O. Ritvos Activation of the Bone Morphogenetic Protein Signaling Pathway Induces Inhibin {beta}B-Subunit mRNA and Secreted Inhibin B Levels in Cultured Human Granulosa-Luteal Cells J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1254 - 1261. [Abstract] [Full Text] [PDF] |
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F. L. Teixeira Filho, E. C. Baracat, T. H. Lee, C. S. Suh, M. Matsui, R. J. Chang, S. Shimasaki, and G. F. Erickson Aberrant Expression of Growth Differentiation Factor-9 in Oocytes of Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1337 - 1344. [Abstract] [Full Text] [PDF] |
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J. G. Hreinsson, J. E. Scott, C. Rasmussen, M. L. Swahn, A. J. W. Hsueh, and O. Hovatta Growth Differentiation Factor-9 Promotes the Growth, Development, and Survival of Human Ovarian Follicles in Organ Culture J. Clin. Endocrinol. Metab., January 1, 2002; 87(1): 316 - 321. [Abstract] [Full Text] [PDF] |
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C. Yan, P. Wang, J. DeMayo, F. J. DeMayo, J. A. Elvin, C. Carino, S. V. Prasad, S. S. Skinner, B. S. Dunbar, J. L. Dube, et al. Synergistic Roles of Bone Morphogenetic Protein 15 and Growth Differentiation Factor 9 in Ovarian Function Mol. Endocrinol., June 1, 2001; 15(6): 854 - 866. [Abstract] [Full Text] [PDF] |
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T. R. Clarke, Y. Hoshiya, S. E. Yi, X. Liu, K. M. Lyons, and P. K. Donahoe Mullerian Inhibiting Substance Signaling Uses a Bone Morphogenetic Protein (BMP)-Like Pathway Mediated by ALK2 and Induces Smad6 Expression Mol. Endocrinol., June 1, 2001; 15(6): 946 - 959. [Abstract] [Full Text] [PDF] |
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