This proposal is designed to identify genetic factors which play a crucial role in the maturation phase of spermatogenesis. The investigator proposes to examine the non-pleiotropic mouse mutant, Lvs (lacking vigorous sperm). This transgene-induced mutation appears to affect spermatogenesis at the time of nuclear condensation and displays two unique properties: genetic dominance and a modifying effect of the genetic background. Light and electron microscopy reveals that spermatogenesis proceeds normally until nuclear condensation, which occurs but gives rise to a variety of abnormally shaped nuclei resulting in male sterility. The mutation is unusual in that it is genetically dominant causing the abnormal phenotype even though a normal copy of the chromosomal region is present. The phenotype is fully penetrant on some common inbred backgrounds (SJL and FVB) but totally non-penetrant on others (C57BL/6 and BALB/c) giving a fully fertile phenotype. Data accumulated to date indicate that this epistatic modification of the Lvs phenotype is due to a single locus. The Specific Aims of this small grant RO3 proposal are to generate molecular data (structural analysis and isolation of putative Lvs gene) which will lay the foundations for a more comprehensive RO1 grant aimed at identifying the Lvs gene, studying its biology, mapping of the putative modifier locus and examining the significance of Lvs in human male infertility.

R03HD037630

1999-06-01

2001-05-31