SEVERE IMPAIRMENT OF SPERMATOGENESIS IN MICE LACKING THE CREM GENE

Spermatogenesis is a complex developmental process that occurs in seve ral phases. A large number of genes have been identified that are expr essed during spermatogenesis(1,2), but the biological significance of many of these is not yet known. We have used gene targeting to selecti vely eliminate the transcription factor CREM (cyclic AMP-responsive el ement modulator), which is thought to be important for mammalian sperm atogenesis(3-5). Male mice deficient for all CREM proteins are sterile , as their developing spermatids fail to differentiate into sperm, and postmeiotic gene expression in the testis declines dramatically. The cessation of sperm development is not accompanied by decreases in the levels of follicle-stimulating hormone or testosterone. Our findings i ndicate that the CREM gene is essential for spermatogenesis, and mice deficient for this transcription factor could serve as a model system for the study of idiopathic infertility in men.