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Temporally Controlled Site-Specific Mutagenesis in the Germ Cell Lineage of the Mouse Testis¹

^a Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Université Louis Pasteur, Collège de France, B.P. 163, 67404 Illkirch-Cedex, Communauté Urbaine de Strasbourg, France

We have obtained a PrP-Cre-ER^T transgenic mouse line (28.8) that selectively expresses in testis the tamoxifen-inducible Cre-ER^T recombinase under the control of a mouse Prion protein (PrP) promoter-containing genomic fragment. Cre-ER^T is expressed in spermatogonia and spermatocytes, but not in Sertoli and Leydig cells. We also established reporter PrP-L-EGFP-L transgenic mice harboring a LoxP-flanked enhanced green fluorescent protein (EGFP) Cre reporter cassette under the control of the same PrP promoter-containing genomic fragment that exhibits prominent EGFP expression in brain and testis. Using the PrP-L-EGFP-L as well as other Cre-reporter mice, we demonstrate that tamoxifen administration efficiently and selectively induces Cre-mediated recombination in the germ cell lineage. The established PrP-Cre-ER^T line should provide a valuable tool for studying functions of germ cell-expressed genes involved in spermatogenesis.

¹ This work was supported by funds from Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Collège de France, Hôpital Universitaire de Strasbourg, Association pour la Recherche sur le Cancer, Fondation pour la Recherche Médicale, Human Frontier Science Program, Ministère de l'Education Nationale de la Recherche et de la Technologie, and the European Community. P.W. was supported by a fellowship (823A-056725) from the Swiss National Science Foundation. M.S. was supported by a Marie Curie Individual Fellowship (1999-01507).

² Correspondence: Pierre Chambon, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut National de la Santé et de la Recherche Médicale/Centre National de la Recherche Scientifique/Université Louis Pasteur, Boîte Postale 163, 67404 Illkirch Cedex, Communauté Urbaine de Strasbourg, France. FAX: 33 3 88 65 32 03; chambon{at}igbmc.u-strasbg.fr

³ Current address: Brain Research Institute, University and ETH Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland

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