Abnormal Sperm in Mice Lacking the Taf7l Gene

Abstract

TFIID is a general transcription factor required for transcription of most protein-coding genes by RNA polymerase II. TAF7L is an X-linked germ cell-specific paralogue of TAF7, which is a generally expressed component of TFIID. Here, we report the generation of Taf7l mutant mice by homologous recombination in embryonic stem cells by using the Cre-loxP strategy. While spermatogenesis was completed in Taf7l^−/Y mice, the weight of Taf7l^−/Y testis decreased and the amount of sperm in the epididymides was sharply reduced. Mutant epididymal sperm exhibited abnormal morphology, including folded tails. Sperm motility was significantly reduced, and Taf7l^−/Y males were fertile with reduced litter size. Microarray profiling revealed that the abundance of six gene transcripts (including Fscn1) in Taf7l^−/Y testes decreased more than twofold. In particular, FSCN1 is an F-action-bundling protein and thus may be critical for normal sperm morphology and sperm motility. Although deficiency of Taf7l may be compensated in part by Taf7, Taf7l has apparently evolved new specialized functions in the gene-selective transcription in male germ cell differentiation. Our mouse studies suggest that mutations in the human TAF7L gene might be implicated in X-linked oligozoospermia in men.

SUPPLEMENTAL MATERIAL

We thank J. R. McCarrey for germ cell preparations, J. Tobias for microarray data analysis, Q. C. Yu for electron microscopy, and D. Yu for help in real-time PCR analysis. We thank F. Yang and J. Pan for technical contributions and comments on the manuscript.

This study was supported by the University of Pennsylvania Research Foundation and NIH/NICHD grant HD 045866 (P.J.W.), NIH grant 1-R01-HD41552 (G.L.G.), Fogarty International Center grant NIH 5-D43-TW 00671 (M.G.B.), and the Howard Hughes Medical Institute (D.C.P). Work at the IGBMC (I.D) was supported by grants from the CNRS, the INSERM, the Fondation pour la Recherche Médicale, the Ministère de la Recherche et de la Technologie, the European Union RTN-00026, the Association pour la Recherche contre le Cancer, and the Ligue Nationale contre le Cancer. M.K. was a recipient of a fellowship from the Fondation pour la Recherche Médicale.