MODULAR ELEMENTS OF THE MLC 1F 3F LOCUS CONFER FIBER-SPECIFIC TRANSCRIPTION REGULATION IN TRANSGENIC MICE/

The two proteins encoded by the fast alkali myosin light chain (MLC) 1 f/3f locus are developmentally regulated, muscle specific, and express ed exclusively in fast-twitch fibers. Their expression is independentl y regulated by two separate promoters and a downstream enhancer. Previ ous studies showed a reporter gene directed by the rat MLC 1f promoter and MIC enhancer to exhibit correct skeletal muscle-specific expressi on in transgenic mice during development and to be preferentially expr essed in fast-twitch Type IIB fibers [Donoghue et al., (1991) J. Cell Biol. 115:423-434]. The MIC 3f promoter also directed muscle-specific expression of a CAT reporter gene in adult transgenic mice and showed little dependence upon the enhancer. Here, we show that the MIC 3f pro moter also directs transgene expression in the fast-twitch fibers of a dult skeletal muscle, but almost exclusively to fiber Types IIA and II X. MLC 3f transgene expression occurs in only a subset of the fiber ty pes that express the endogenous locus, indicating modular elements inc luded in the transgene confer fiber-specific transcription regulation. MyoD protein was also found to be restricted to fiber Types IIA and I IX, providing evidence for its possible role in mediating fiber-specif ic gene expression. (C) 1996 Wiley-liss, Inc.