CYCLIN A1 IS REQUIRED FOR MEIOSIS IN THE MALE-MOUSE

The mammalian A-type cyclin family consists of two members. cyclin Al (encoded by Ccna1) and cyclin AZ (encoded by Ccna2). Cyclin AZ promote s both G1/S and G2/M transitions(1,2), and targeted deletion of Ccna2 in mouse is embryonic lethal(3). Cyclin Al is expressed in mice exclus ively in the germ cell lineage(4) and is expressed in humans at highes t levels in the testis and certain myeloid leukaemia cells(5,6). To in vestigate the role of cyclin Al and possible redundancy among the cycl ins in vivo, we generated mice bearing a null mutation of Ccna1. Ccna1 (-/-) males were sterile due to a block of spermatogenesis before the first meiotic division, whereas females were normal. Meiosis arrest in Ccna1(-/-) males was associated with increased germ cell apoptosis, d esynapsis abnormalities and reduction of Cdc2 kinase activation at the end of meiotic prophase. Cyclin Al is therefore essential for spermat ocyte passage into the first meiotic division in mate mice, a function that cannot be complemented by the concurrently expressed B-type cycl ins.