EXPRESSION OF THE SM22-ALPHA PROMOTER IN TRANSGENIC MICE PROVIDES EVIDENCE FOR DISTINCT TRANSCRIPTIONAL REGULATORY PROGRAMS IN VASCULAR ANDVISCERAL SMOOTH-MUSCLE CELLS

SM22 alpha is a putative calcium-binding protein that is expressed in cardiac, smooth, and skeletal muscle lineages during mouse embryogenes is and in adult smooth muscle cells (SMC). To define the mechanisms th at regulate smooth muscle-specific gene transcription, we isolated the SM22 alpha gene and analyzed its 5'-flanking region for elements that direct smooth muscle expression in transgenic mice. Using a series of promoter deletions, a region of the SM22 alpha promoter containing 44 5 base pairs of 5'-flanking sequence was found to be sufficient to dir ect the specific expression of a lacZ transgene in mouse embryos in th e vascular smooth, cardiac, and skeletal muscle lineages in a temporos patial pattern similar to that of the endogenous SM22 alpha gene. Howe ver, in contrast to the endogenous gene, transgene expression was not detected in venous, nor visceral SMCs. This SM22 alpha-lacZ transgene was therefore able to distinguish between the transcriptional regulato ry programs that control gene expression in vascular and visceral SMCs and revealed heretofore unrecognized differences between these SMC ty pes. These results suggest that distinct transcriptional regulatory pr ograms control muscle gene expression in vascular and visceral SMCs.