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Cyclin A1 is required for meiosis in the male mouse

Abstract

The mammalian A-type cyclin family consists of two members, cyclin A1 (encoded by Ccna1 ) and cyclin A2 (encoded by Ccna2 ). Cyclin A2 promotes both G1/S and G2/M transitions1,2, and targeted deletion of Ccna2 in mouse is embryonic lethal3. Cyclin A1 is expressed in mice exclusively in the germ cell lineage4 and is expressed in humans at highest levels in the testis and certain myeloid leukaemia cells5,6. To investigate the role of cyclin A1 and possible redundancy among the cyclins 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, desynapsis abnormalities and reduction of Cdc2 kinase activation at the end of meiotic prophase. Cyclin A1 is therefore essential for spermatocyte passage into the first meiotic division in male mice, a function that cannot be complemented by the concurrently expressed B-type cyclins.

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Figure 1: Targeted disruption of mouse Ccna1.
Figure 2: Spermatogenesis abnormalities in Ccna1–/– mice.
Figure 3: Evaluation of gene expression during spermatogenesis and determination of the meiotic arrest of Ccna1–/– males.
Figure 4: Detection of germ cell apoptosis.
Figure 5: Histone H1 kinase assay of Cdc2, Cdk2 and cyclin B1 (B1) immunoprecipitates.

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Acknowledgements

We thank M. Carrington for providing affinity-purified cyclin A1 antibody, X.Y. Wang and C. Marshall for technical assistance and T.R. Kumar for critical reading of the manuscript. This work was supported by National Institute of Health research grants to D.J.W. and M.M.M.

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Correspondence to Debra J. Wolgemuth..

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Liu, D., Matzuk, M., Sung, W. et al. Cyclin A1 is required for meiosis in the male mouse. Nat Genet 20, 377–380 (1998). https://doi.org/10.1038/3855

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