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Molecular and Cellular Biology, February 2007, p. 1146-1157, Vol. 27, No. 3
0270-7306/07/$08.00+0 doi:10.1128/MCB.01009-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.
URA 2578 CNRS Institut Pasteur, 25, rue du Docteur Roux, 75724 Paris Cedex 15, France,1 CNRS UMR6061 Génétique et Développement, Université de Rennes 1, IFR140, 2 Av Léon Bernard, CS 34317, 35043 Rennes, France2
Received 6 June 2006/ Returned for modification 13 July 2006/ Accepted 18 November 2006
CUG-BP1/CELF1 is a multifunctional RNA-binding protein involved in the regulation of alternative splicing and translation. To elucidate its role in mammalian development, we produced mice in which the Cugbp1 gene was inactivated by homologous recombination. These Cugbp1/ mice were viable, although a significant portion of them did not survive after the first few days of life. They displayed growth retardation, and most Cugbp1/ males and females exhibited impaired fertility. Male infertility was more thoroughly investigated. Histological examination of testes from Cugbp1/ males showed an arrest of spermatogenesis that occurred at step 7 of spermiogenesis, before spermatid elongation begins, and an increased apoptosis. A quantitative reverse transcriptase PCR analysis showed a decrease of all the germ cell markers tested but not of Sertoli and Leydig markers, suggesting a general decrease in germ cell number. In wild-type testes, CUG-BP1 is expressed in germ cells from spermatogonia to round spermatids and also in Sertoli and Leydig cells. These findings demonstrate that CUG-BP1 is required for completion of spermatogenesis.
Published ahead of print on 27 November 2006.
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