Analysis of SM22α-deficient mice reveals unanticipated insights into smooth muscle cell differentiation and function

SM22 alpha is a 22-kDa smooth muscle cell (SMC) lineage-restricted protein that physically associates with cytoskeletal actin filament bundles in contractile SMCs. To examine the function of SM22 alpha, gene targeting was used to generate SM22 alpha -deficient (SM22(-/-LacZ)) mice. The gene targeting strategy employed resulted in insertion of the bacterial lacZ reporter gene at the SM22 alpha initiation codon, permitting precise analysis of the temporal and spatial pattern of SM22 alpha transcriptional activation in the developing mouse. Northern and Western blot analyses confirmed that the gene targeting strategy resulted in a null mutation. Histological analysis of SM22(+/-LacZ) embryos revealed detectable beta -galactosidase activity in the unturned embryonic day 8.0 embryo in the layer of cells surrounding the paired dorsal aortae concomitant with its expression in the primitive heart tube, cephalic mesenchyme, and yolk sac vasculature. Subsequently, during postnatal development, beta -galactosidase activity was observed exclusively in arterial, venous, and visceral SMCs. SM22 alpha -deficient mice are viable and fertile. Their blood pressure and heart rate do not differ significantly front their control SM22 alpha (+/-) and SM22 alpha (+/+) littermates. The vasculature and SMC-containing tissues of SM22 alpha -deficient mice develop normally and appear to be histologically and ultrastructurally similar to those of their control littermates. Taken together, these data demonstrate that SM22 alpha is not required for basal homeostatic functions mediated by vascular and visceral SMCs in the developing mouse. These data also suggest that signaling pathways that regulate SMC specification and differentiation from local mesenchyme are activated earlier in the angiogenic program than previously recognized.