Developmental analysis of the expression of the hypoxanthine phosphoribosyltransferase (Hprt) gene in the mouse testis

An enigmatic feature of mammalian spermatogenesis is the transcriptional inactivation of the X chromosome in meiotic prophase. This study examines aspects and consequences of spermatogenic X-chromosome inactivation in the mouse. Since the X chromosome encodes several housekeeping proteins, serious consequence could arise for the spermatogenic cell in the absence of mechanisms to ensure continued enzymatic function throughout development. The goal of this study was to determine the spermatogenic expression of the X-linked gene for hypoxanthine phosphoribosyltransferase (Hprt) and the relevance of its expression to X-chromosome inactivation. The results demonstrated that HPRT activity is maintained in spermatogenic cells throughout development in spite of X-chromo- some inactivation; however, specific activities of HPRT in meiotic and postmeiotic germ cells were significantly lower than that in premeiotic ones. Maintenance of Hprt transcripts was also demonstrated. Interestingly, the highest level of Hprt transcripts was found in leptotene/zygotene spermatocytes, suggesting a hyper- activation of the Hprt gene and/or accumulation of Hprt transcripts in these cells. The level of Hprt transcripts also appeared to be higher in round spermatids than in pachytene spermatocytes, suggesting a reactivation of the Hprt gene after meiosis. It was also found that the relative abundance of Hprt transcripts in germ-cell-deficient testes of XXSxr mice was much higher than that in meiotic and postmeiotic germ cells even though their activities of HPRT were similar. Examination of the translational status of Hprt transcripts in testes and germ cells revealed that most of the transcript was translationally active in XXSxr testes but not in pachytene iv spermatocytes or round spermatids. Since no functional autosomal Hprt gene exists in the mouse, these data suggest a strategy for maintaining HPRT activity in germ cells throughout development that involves stabilization of gene products coupled to possible hyperactivation of the Hprt gene prior to X-inactivation and reactivation of the gene in postmeiotic cells.