MEIOTIC CELL-CYCLE REQUIREMENT FOR A FLY HOMOLOG OF HUMAN DELETED IN AZOOSPERMIA

INFERTILITY resulting from a severe defect in sperm production affects 2% of men worldwide(1,2). Of these men with azoospermia, the absence of sperm in semen, one in eight carry de novo deletions for a specific region of the Y chromosome(3-5). A candidate gene for the Y-chromosom e azoospermia factor (AZF) has been identified and named Deleted in Az oospermia (DAZ)(5). Here we describe the cloning and characterization of the Drosophila gene boule, which is a homologue of DAZ. The two gen es encode closely related proteins that contain a predicted RNA-bindin g motif, and both loci are expressed exclusively in the testis. Loss o f bottle function results in azoospermia; meiotic divisions are blocke d, although limited spermatid differentiation occurs. Histological exa mination of boule testes with cell-cycle markers indicates that the pr imary defect is at the meiotic G2/M transition. These results support the hypothesis that DAZ is the human AZF, and indicate that Boule and DAZ have an essential meiotic function in fly and human spermatogenesi s.