Selective expression of Cre recombinase in skeletal muscle fibers

• Published in: Genesis (New York, N.Y. : 2000) Vol. 26; no. 2; pp. 165 - 166
• Main Authors: Bothe, Gerald W. M., Haspel, Jeffrey A., Smith, Cynthia L., Wiener, Heidi H., Burden, Steven J.
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01.02.2000
• Subjects: Animals; erbB gene; ErbB-2 protein; ErbB-4 protein; Integrases - metabolism; Mice; Mice, Inbred C57BL; Mice, Transgenic; Muscle Fibers, Skeletal - enzymology; Muscle, Skeletal - enzymology; myc 1f gene; neuregulin; Viral Proteins
• ISSN: 1526-954X; 1526-968X
• DOI: 10.1002/(SICI)1526-968X(200002)26:2<165::AID-GENE22>3.0.CO;2-F

It is often difficult to study the function of genes that are widely expressed, because their critical function in one tissue can complicate or preclude study of their role in other tissues. Several lines of evidence support the idea that neuregulin (NRG) may be a synaptic signal that activates expression of certain genes in muscle nuclei positioned near the synaptic site (Burden, 1998). Since mice lacking NRG, or its receptors (ErbB2 or ErbB4) die, owing to a failure of cardiac differentiation (Lee et al., 1995; Gasmann et al., 1995; Meyer and Birchmeier, 1995), similar to four days prior to neuromuscular synapse formation, it remains unclear whether NRG-mediated signaling is indeed required for synapse-specific gene expression. To determine the role of NRG-mediated signaling in neuromuscular synapse formation and to circumvent the problems associated with the early requirement for NRG-mediated signaling in early development, we sought to inactivate erbB genes selectively in skeletal muscle cells, using the Cre/loxP recombination system (Gu et al., 1994). These experiments require producing mice that selectively express Cre recombinase in skeletal muscle cells and crossing these mice with mice that carry an erbB target gene containing loxP sites flanking a critical exon. Although transgenic mice expressing Cre in heart and skeletal muscle cells have been described (Bruning et al., 1998), we are unaware of mice that express Cre selectively in skeletal muscle cells. Because the myosin light chain 1f (mlc 1f) gene is expressed strongly and selectively in skeletal muscle cells, beginning early during muscle development (Lyons et al., 1990), we chose to introduce cre into the mlc 1f locus by homologous recombination.