The broad, long-term objective of the present application is to study a novel regulatory pathway of gene expression in mouse spermiogenesis that could be exploited for development of novel male contraceptives. Spermiogenesis is a complex differentiation process by which haploid germ cells transform into mature spermatozoa. In the past few years, genetic studies in mice have identified four genes that cause a global arrest in early spermiogenesis when deleted in mice, and these genes constitute a group of key regulators of spermiogenesis (CREM, TRF2, MIWI, and TPAP). In this project, we will characterize a novel key regulator of spermiogenesis named RNF17 in mice.
Our specific aims are: 1) Knockout mice will be generated and characterized to study the regulation of spermiogenesis; 2) Proteins interacting with the novel key regulator will be screened using the yeast 2-hybrid system, and will be characterized biochemically and cell biologically; 3) Genes transcriptionally regulated by the novel key regulator will be identified by the gene array technology using both the Affymetrix mouse gene chips and our own germ cell microarrays. Our ? proposed genetic, biochemical and genomics experiments will define a novel regulatory network of gene expression in mouse spermiogenesis, will have implications in molecular etiology of male infertility in humans, and will provide critical information about regulation of spermiogenesis that could be explored for developing reversible male contraceptive leads with minimal side effects. ? ?

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZHD1-DRG-D (28))
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Blithe, Diana
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University of Pennsylvania
Veterinary Sciences
Schools of Veterinary Medicine
United States
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