Temporally controlled targeted somatic mutagenesis in skeletal muscles of the mouse

To generate temporally controlled targeted somatic mutations selectively and efficiently in skeletal muscles, we established a transgenic HSA-Cre-ERT2 mouse line in which the expression of the tamoxifen-dependent Cre-ERT2 recombinase is under the control of a large genomic DNA segment of the human skeletal muscle a-actin gene, contained in a P1-derived artificial chromosome. In this transgenic line Cre-ERT2 is selectively expressed in skeletal muscles, and Cre-ERT2-mediated alteration of LoxP flanked (floxed) target genes is skeletal muscle-specific and strictly tamoxifen-dependent. HSA-Cre-ERT2 mice should be of great value to analyze gene function in skeletal muscles, and to establish animal models of human skeletal muscle disorders. (c) 2005 Wiley-Liss, Inc.