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This version published online on December 27, 2006
Molecular Endocrinology, doi:10.1210/me.2006-0332
Molecular Endocrinology Vol. 0, No. 2006 200603321-
doi:10.1210/me.2006-0332
Copyright © 2006 by the Endocrine Society.
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Submitted on August 11, 2006
Accepted on December 19, 2006

Differential functions of the Aurora-B and Aurora-C kinases in mammalian spermatogenesis

Sarah Kimmins, Claudia Crosio, Noora Kotaja, Jun Hirayama, Lucia Monaco, Christer Höög, Marcel van Duin, Jan A. Gossen, and Paolo Sassone-Corsi*

Departments of Animal Science and Pharmacology, McGill University, Montreal, Canada (S.K.); Fondazione Santa Lucia IRCCS, Rome, Italy (C.C); Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland (N.K.); Department of Pharmacology, School of Medicine University of California Irvine, Irvine, California (J.H. and P.S.-C.); Center for Genomics and Bioinformatics, Karolinska Institutet Berzelius väg 35, S-171 77 Stockholm, Sweden (C.H.)l Dept. Human Physiology and Pharmacology, University of Rome "La Sapienza"P.le Aldo Moro 5. 00185 Rome, Italy (L.M.); Department of Target Discovery, NV Organon, N.V, BH Oss, The Netherlands (J.A.G and M.D.)

* To whom correspondence should be addressed. E-mail: psc{at}uci.edu.

The Aurora kinases are cell cycle regulatory serine-threonine kinases that have been implicated in the function of the centrosomes, kinetechores, chromosome dynamics and cytokinesis. In comparison to other tissues, there are high levels of expression of Aurora-B and C in testis. An open question is their respective role in mammalian spermatogenesis. Here we describe the expression and distribution patterns of the three kinases in mouse testis using in situ hybridization and immunohistochemistry. Importantly, the localization of Aurora-B is tightly regulated during spermatogenesis, while Aurora-C expression appears to be testis-specific. To address the function of Aurora-B in spermatogenesis we have generated transgenic mice using a pachytene-stage specific promoter driving the expression of either wild-type Aurora-B, or of an inactive form of the kinase. Expression of the inactive Aurora-B results in abnormal spermatocytes, increased apoptosis, spermatogenic arrest and subfertility defects. The function of Aurora-C may also be targeted in the Aurora-B transgenic mutants. To address the function of Aurora-C in testis, we generated Aurora-C knockout mice by homologous recombination. Remarkably, Aurora-C null mice were viable, yet the males had compromised fertility. Aurora-C mutant sperm display abnormalities which included heterogenous chromatin condensation, loose acrosomes and blunted heads. These findings indicate that Aurora-B and Aurora-C serve specialized functions in mammalian spermatogenesis.
Key words: spermatogenesis • Aurora Kinase • fertility • testis




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