This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this project is to characterize repro27 mice, a model of male infertility. Preliminary data suggests that the repro27 phenotype is caused by a point mutation in the Golga3 gene. Golga3 encodes a golgi autoantigen, a member of the golgin protein family. The GOLGA3 protein is important for the redistribution of the Golgi apparatus during mitosis, plays a role in apoptosis, and is required sperm development. Roughly 15% of couples in the US experience problems conceiving and about half are of male origin. It is hypothesized that genetic defects leading to abnormalities in sperm number, motility, and morphology may account for a significant percentage of idiopathic male infertility. Genetic mouse models provide valuable in vivo tools to study the regulation of mammalian reproduction. Approximately 99% of the roughly 40,000 genes within the two genomes are conserved between mice and humans and thus, genes important for regulation of spermatogenesis are likely conserved between the two species. repro27 is a genetic mouse model produced using the chemical mutagen ethylnitrosourea. The mutation is recessively inherited and male specific. Male homozygotes have very low testis weight, very low epididymal sperm concentration, abnormally shaped sperm heads without tails, very low motility, and no success with in vitro fertilization. Sperm development is initially normal but testes begin to lose germ cells beginning just after 2 weeks of age.
The specific aims of this research are to: (1) conduct a morphological and histological characterization; (2) characterize gene expression patterns to define the molecular defects; and (3) DNA sequence candidate genes. In summary, characterization of genetic models of male infertility increases our understanding of germ cell development. Identification of the mechanisms responsible for the novel repro27 mouse model will ultimately aid in deciphering the causes of male infertility in humans.
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