Cyclin A1 protein shows haplo-insufficiency for normal fertility in male mice

Abstract

In higher eukaryotes, the cyclins constitute a family of proteins involved in progression through the cell cycle. The cyclin A1 gene (Ccna1) is expressed during meiosis and is required for spermatogenesis. Targeted disruption of theCcna1gene with aLacZreporter gene has allowed us to study the expression pattern of this gene in more detail. We have confirmed expression in mouse pre-meiotic spermatocytes and also detected expression in the accessory olfactory bulb, hippocampus and amygdala of the adult brain. We have also found that the amount of cyclin A1 protein influences the fertility of male mice and its action is modulated by genetic background. On an outbred genetic background (129S6/SvEv × MF1),Ccna1^tm1Col−/− animals are sterile due to spermatogenic arrest prior to the first meiotic division whileCcna1^tm1Col+/− mice show reduced sperm production and fertility. This is even more pronounced on an inbred genetic background (129S6/SvEv) whereCcna1^tm1Col+/− male mice are sterile due to a severe reduction in the total number of sperm.