1. Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75235-9038, USA

Abstract

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-chromosome azoospermia factor (AZF) has been identified and named Deleted in Azoospermia (DAZ)⁵. Here we describe the cloning and characterization of the Drosophila gene boule, which is a homologue of DAZ. The two genes encode closely related proteins that contain a predicted RNA-binding motif, and both loci are expressed exclusively in the testis. Loss of boule function results in azoospermia; meiotic divisions are blocked, although limited spermatid differentiation occurs. Histological examination of boule testes with cell-cycle markers indicates that the primary 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 spermatogenesis.