DAZAP1, an hnRNP protein, is required for normal growth and spermatogenesis in mice

DAZAP1 (Deleted in Azoospermia Associated Protein 1) is a ubiquitous hnRNP protein that is expressed most abundantly in the testis. Its ability to shuttle between the nucleus and the cytoplasm and its exclusion from the transcriptionally inactive XY body in pachytene spermatocytes implicate it in mRNA transcription and transport. We generated Dazap1 mutant alleles to study the role of DAZAP1 in mouse development. Most mice homozygous for the null allele as well as a hypomorphic Fn allele died soon after birth. The few Dazap1(Fn/Fn) mice that survived could nonetheless live for more than a year. They appeared and behaved normally but were much smaller in size compared to their wild-type and heterozygous littermates. Both male and female Dazap1(Fn/Fn) mice were sterile. Males had small testes, and the seminiferous tubules were atrophic with increased numbers of apoptotic cells. The tubules contained many germ cells, including pachytene spermatocytes with visible XY-bodies and diplotene spermatocytes, but no post-meiotic cells. FACS analyses confirmed the absence of haploid germ cells, indicating spermatogenesis arrested right before the meiotic division. Female Dazap1(Fn/Fn) mice had small ovaries that contained normal-appearing follicles, yet their pregnancy produced no progeny due to failure in embryonic development. The phenotypes of Dazap1 mutant mice indicate that DAZAP1 is not only essential for spermatogenesis, but also required for the normal growth and development of mice.