The goals of this project are to characterize phenotypes of spermatogenesis mutants and to develop resource for gene expression analysis of spermatogenesis and cell-cell interaction in the testis. With whole-genome mutagenesis and screening for infertility mutants, there is now opportunity to bring unprecedented mutant resources to the reproductive biology community. In this project a detailed analysis of the phenotypes of induced mutations that affect spermatogenesis and sperm function will be conducted by studying testis and germ-cell morphology, gene expression and function of sperm in fertilization in vitro. A more detailed analysis of mutants impaired in meiotic cell-cycle progress or characterized by elevated sperm aneuploidy will involve localization of meiotically important proteins, test of nuclear competence for the meiotic division and analysis of germ-cell autonomy of mutant gene action. These analyses are essential first steps, forming a solid foundation for follow-on investigations, and may also suggest candidate genes to guide the gene cloning efforts (Project by Schimenti). Molecular characterization of spermatogenesis mutants will require analysis of gene expression profiles of spermatogenic cells and their supporting Sertoli cells. Thus, the focus off the second goal is to build resources for expression profiling of mutants. Marker gene sequences,, characteristic of spermatogenic stages and of Sertoli cell response to spermatocyte co-culture, will be identified and used for phenotype characterization of induced male sterility mutants. By these two goals this project will contribute to the program's overall effect of discovering and defining the functional genomics of gametogenesis.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
1P01HD042137-01
Application #
6606594
Study Section
Special Emphasis Panel (ZHD1)
Project Start
2002-09-01
Project End
2007-06-30
Budget Start
Budget End
Support Year
1
Fiscal Year
2002
Total Cost
Indirect Cost
Name
Jackson Laboratory
Department
Type
DUNS #
042140483
City
Bar Harbor
State
ME
Country
United States
Zip Code
04609
Hays, E; Majchrzak, N; Daniel, V et al. (2017) Spermatogenesis associated 22 is required for DNA repair and synapsis of homologous chromosomes in mouse germ cells. Andrology 5:299-312
Fujiwara, Yasuhiro; Matsumoto, Hirokazu; Akiyama, Kouyou et al. (2015) An ENU-induced mutation in the mouse Rnf212 gene is associated with male meiotic failure and infertility. Reproduction 149:67-74
Sun, Fengyun; Fujiwara, Yasuhiro; Reinholdt, Laura G et al. (2015) Nuclear localization of PRDM9 and its role in meiotic chromatin modifications and homologous synapsis. Chromosoma 124:397-415
Pattabiraman, Shrivatsav; Baumann, Claudia; Guisado, Daniela et al. (2015) Mouse BRWD1 is critical for spermatid postmeiotic transcription and female meiotic chromosome stability. J Cell Biol 208:53-69
Harris, Tanya P; Schimenti, Kerry J; Munroe, Robert J et al. (2014) IQ motif-containing G (Iqcg) is required for mouse spermiogenesis. G3 (Bethesda) 4:367-72
Li, Xin Zhiguo; Roy, Christian K; Dong, Xianjun et al. (2013) An ancient transcription factor initiates the burst of piRNA production during early meiosis in mouse testes. Mol Cell 50:67-81
Liu, Ye; Zaun, Hans C; Orlowski, John et al. (2013) CHP1-mediated NHE1 biosynthetic maturation is required for Purkinje cell axon homeostasis. J Neurosci 33:12656-69
Fujiwara, Yasuhiro; Ogonuki, Narumi; Inoue, Kimiko et al. (2013) t-SNARE Syntaxin2 (STX2) is implicated in intracellular transport of sulfoglycolipids during meiotic prophase in mouse spermatogenesis. Biol Reprod 88:141
Schimenti, Kerry J; Feuer, Sky K; Griffin, Laurie B et al. (2013) AKAP9 is essential for spermatogenesis and sertoli cell maturation in mice. Genetics 194:447-57
Gómez, Rocío; Jordan, Philip W; Viera, Alberto et al. (2013) Dynamic localization of SMC5/6 complex proteins during mammalian meiosis and mitosis suggests functions in distinct chromosome processes. J Cell Sci 126:4239-52

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