Abstract

The long-term objective of the current application is to study the regulation of meiosis in mice. Abnormality in meiosis is a leading cause of birth defects and infertility in humans. Genomics studies in mice showed that the X chromosome is enriched for genes involved in early spermatogenesis. The current application is to study the role of a mouse X-linked testis-specific gene product, TEX11, in meiosis of both sexes. The TEX11 protein is conserved in mice and humans.
Our specific aims are: 1) To characterize defects in meiotic recombination and chromosomal synapsis in TEX11-deficient males;2) To investigate the role of TEX11 in oocyte aneuploidy and embryo death;3) To study the role of TEX11 in linking meiotic recombination with the synaptonemal complex. Our proposed genetic, cell and molecular biological studies will help to uncover the mechanism underlying the regulation of meiosis in both sexes by TEX11. Our research will also provide insight into the molecular etiology of X-linked male infertility and birth defects (trisomy and monosomy) in humans.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM076327-03
Application #
7682975
Study Section
Cellular, Molecular and Integrative Reproduction Study Section (CMIR)
Program Officer
Haynes, Susan R
Project Start
2007-09-20
Project End
2011-08-31
Budget Start
2009-09-01
Budget End
2010-08-31
Support Year
3
Fiscal Year
2009
Total Cost
$299,250
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Luo, Mengcheng; Zhou, Jian; Leu, N Adrian et al. (2015) Polycomb protein SCML2 associates with USP7 and counteracts histone H2A ubiquitination in the XY chromatin during male meiosis. PLoS Genet 11:e1004954
Yang, Fang; Silber, Sherman; Leu, N Adrian et al. (2015) TEX11 is mutated in infertile men with azoospermia and regulates genome-wide recombination rates in mouse. EMBO Mol Med 7:1198-210
Zhou, Jian; Stein, Paula; Leu, N Adrian et al. (2015) Accelerated reproductive aging in females lacking a novel centromere protein SYCP2L. Hum Mol Genet 24:6505-14
Zhou, Jian; Leu, N Adrian; Eckardt, Sigrid et al. (2014) STK31/TDRD8, a germ cell-specific factor, is dispensable for reproduction in mice. PLoS One 9:e89471
Zhou, Jian; Goldberg, Ethan M; Leu, N Adrian et al. (2014) Respiratory failure, cleft palate and epilepsy in the mouse model of human Xq22.1 deletion syndrome. Hum Mol Genet 23:3823-9
Zhou, Jian; McCarrey, John R; Wang, P Jeremy (2013) A 1.1-Mb segmental deletion on the X chromosome causes meiotic failure in male mice. Biol Reprod 88:159
Luo, Mengcheng; Yang, Fang; Leu, N Adrian et al. (2013) MEIOB exhibits single-stranded DNA-binding and exonuclease activities and is essential for meiotic recombination. Nat Commun 4:2788
Berkowitz, Karen M; Sowash, Aislinn R; Koenig, Lydia R et al. (2012) Disruption of CHTF18 causes defective meiotic recombination in male mice. PLoS Genet 8:e1002996
Zhou, Jian; Yang, Fang; Leu, N Adrian et al. (2012) MNS1 is essential for spermiogenesis and motile ciliary functions in mice. PLoS Genet 8:e1002516
Zhou, Jian; Pan, Jieyan; Eckardt, Sigrid et al. (2011) Nxf3 is expressed in Sertoli cells, but is dispensable for spermatogenesis. Mol Reprod Dev 78:241-9

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