Growth and differentiation factor 3/Vg-1-related protein (GDF-3/Vgr-2), activin BA and activin BB are members of the transforming growth factor beta superfamily. Members of this superfamily play important roles in a variety of developmental processes. In an effort to aid in the characterization of proteins from this superfamily, the candidate intends to study the functions of GDF-3/Vgr-2 and the activins using the following strategies: In phase I of this proposal the aims are: (1) To further characterize the GDF-3/Vgr-2 gene by studying the pattern of transcription from this gene, and to determine the conservation of this gene among species; (2) To analyze the expression pattern of GDF-3/Vgr-2 mRNA in the developing mouse embryo and in adult mouse tissues by in situ hybridization; (3) To inactivate the GDF-3/Vgr-2 gene by homologous recombination in embryonic stem cells. (4) To substitute the activin BA mature region with activin BB to determine if these proteins are functionally interchangeable. In phase II of this proposal the aims are: (1) To continue to characterize the morphologic, histologic and biochemical characteristics of the mutant mice produced during phase 1; and (2) To crossbreed mice carrying a mutation in the GDF-3/Vgr-2 locus with other mice deficient in bone morphogenetic proteins and activins.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Clinical Investigator Award (CIA) (K08)
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Maternal and Child Health Research Committee (HDMC)
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Baylor College of Medicine
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Zamani, Nader; Brown, Chester W (2011) Emerging roles for the transforming growth factor-{beta} superfamily in regulating adiposity and energy expenditure. Endocr Rev 32:387-403
Mithraprabhu, Sridurga; Mendis, Sirisha; Meachem, Sarah J et al. (2010) Activin bioactivity affects germ cell differentiation in the postnatal mouse testis in vivo. Biol Reprod 82:980-90
Bournat, Juan C; Brown, Chester W (2010) Mitochondrial dysfunction in obesity. Curr Opin Endocrinol Diabetes Obes 17:446-52
Shen, Joseph J; Huang, Lihua; Li, Liunan et al. (2009) Deficiency of growth differentiation factor 3 protects against diet-induced obesity by selectively acting on white adipose. Mol Endocrinol 23:113-23
Li, Liunan; Shen, Joseph J; Bournat, Juan C et al. (2009) Activin signaling: effects on body composition and mitochondrial energy metabolism. Endocrinology 150:3521-9
Itman, Catherine; Small, Chris; Griswold, Michael et al. (2009) Developmentally regulated SMAD2 and SMAD3 utilization directs activin signaling outcomes. Dev Dyn 238:1688-700
Chen, Canhe; Ware, Stephanie M; Sato, Akira et al. (2006) The Vg1-related protein Gdf3 acts in a Nodal signaling pathway in the pre-gastrulation mouse embryo. Development 133:319-29
Loveland, K L; Hogarth, C; Mendis, S et al. (2005) Drivers of germ cell maturation. Ann N Y Acad Sci 1061:173-82
Brown, Chester W; Li, Liunan; Houston-Hawkins, Dianne E et al. (2003) Activins are critical modulators of growth and survival. Mol Endocrinol 17:2404-17
Chang, Hua; Brown, Chester W; Matzuk, Martin M (2002) Genetic analysis of the mammalian transforming growth factor-beta superfamily. Endocr Rev 23:787-823

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