The design of this proposal seeks to understand the location, structure, and function of mei2, one gene (of several) identified in a recent genome wide screen for chemically-induced mutations affecting meiosis and gametogenesis in mammals. To achieve this, I propose to positionally clone and functionally characterize the induced allele which causes a defect in spermatogenesis. The gene will be genetically mapped, positionally cloned and characterize as to the timing and cellular location of its expression and therefore blocks gamete production, it is particular interest to the field of reproductive biology. However, many of the genes involved in meiosis have also been implicated in facilitating the correct recombination, repair, and structure of chromosomes, giving this proposal blood application to the fields of cancer research and inherited genetic disorders. This proposal makes use of the mouse as a model system with the ultimate goal of understanding similar biology in human beings. Results generated from this work could impact the development of diagnostics and treatments of reproductive conditions, cancers, and disorders resulting from chromosomal aberrations.
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 |
Ward, Jeremy O; Reinholdt, Laura G; Motley, William W et al. (2007) Mutation in mouse hei10, an e3 ubiquitin ligase, disrupts meiotic crossing over. PLoS Genet 3:e139 |
Ward, Jeremy O; Reinholdt, Laura G; Hartford, Suzanne A et al. (2003) Toward the genetics of mammalian reproduction: induction and mapping of gametogenesis mutants in mice. Biol Reprod 69:1615-25 |