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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
1R03HD037630-01
Application #
2850090
Study Section
Mammalian Genetics Study Section (MGN)
Program Officer
Tasca, Richard J
Project Start
1999-06-01
Project End
2001-05-31
Budget Start
1999-06-01
Budget End
2000-05-31
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030