Human cytomegalovirus IE1 promoter/enhancer drives variable gene expression in all fiber types in transgenic mouse skeletal muscle

We produced two lines of transgenic mice carrying the CMV IE1/ β-galactosidase construct CMVLacZ, and analyzed transgene expression and fiber type by histochemical analysis of hindlimb muscle sections. In both lines CMVLacZ was expressed in all four major fiber types: type I (slow) and types IIA, IIB and IIX (fast). There was no unique pattern of fiber-type-preferential expression; fiber-type quantitative differences were observed but details varied between muscle regions and between lines. Both lines showed similar fiber-type-independent regional differences in overall expression levels, and a high level of within-fiber-type variability of expression, even among nearby fibers. The soleus muscle showed strong expression and comparatively little within-fiber-type or between-fiber-type variability.The CMV IE1 promoter/enhancer is not fiber-type-restricted and can be useful for driving germ-line transgene expression in all four fiber types. However, not all fibers express the gene at high levels due in part to regional differences in overall expression levels, and to a high level of within-fiber-type variability. Given the multinucleate syncitial nature of muscle fibers, it is not likely that this variability is due to variegating heterochromatinization. The soleus muscle would make a suitable subject for near-uniform experimental gene expression driven by CMV IE1 elements.Versatile genetic manipulation of skeletal muscle through expression of experimental germ-line transgenes requires knowledge of the expression characteristics of diverse promoter/enhancer elements in the various skeletal muscle fiber types.Rodent limb and axial muscles contain four major fiber types, one slow-contracting (type I) and three fast-contracting (types IIA, IIB, and IIX (also called IID)), that differ in activity patterns [1] and in contractile and metabolic properties [2,3,4,5]. Each of the four principal fiber types expresses a distinct myosin heavy chain gene that largely determines fas