GASZ IS ESSENTIAL FOR MEIOTIC PROGRESSION DURING SPERMATOGENESIS

Abstract

GASZ is a germ cell-specific gene encoding a protein containing four ankyrin repeats, a sterile-alpha motif, and a basic leucine zipper domain. To clarify the in vivo function of GASZ in mice, we generated GASZ null mice through homologous recombination in ES cells. Whereas female mice lacking GASZ possess normal fertility, male mice null for GASZ are viable and grossly normal but demonstrate sterility due to a pre-meiotic arrest in spermatogenesis leading to complete absence of post-meiotic germ cells and loss of testicular mass ( less than 25% compared to WT ). By light microscopy of testis sections, the earliest defects start at 10 days of age. Null mice reveal a delay at the pre-leptotene to leptotene spermatocyte stage suggesting a block in cell-cycle progression (G2-M). This delay is more pronounced in 12 day-old null mice. For adult GASZ-null mice, the most advanced germ cell types resemble early spermatocytes up to zygotene stages, and some tubules display complete depletion of spermatocytes. It is clear that there is a blockade between the preleptotene to leptotene transition, which occurs in the first cycle of spermatogenesis and lasts until adulthood. Thus, GASZ plays an important role in male reproduction. We are continuing to understand how GASZ functions in male germ cells. This study is supported by the National Institutes of Health Specialized Cooperative Centers Program in Reproduction Research (HD07495). (poster)