Analysis of SM22 alpha-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 cont ractile SMCs. To examine the function of SM22 alpha, gene targeting was use d to generate SM22 alpha -deficient (SM22(-/-LacZ)) mice. The gene targetin g strategy employed resulted in insertion of the bacterial lacZ reporter ge ne at the SM22 alpha initiation codon, permitting precise analysis of the t emporal and spatial pattern of SM22 alpha transcriptional activation in the developing mouse. Northern and Western blot analyses confirmed that the ge ne 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 hear t tube, cephalic mesenchyme, and yolk sac vasculature. Subsequently, during postnatal development, beta -galactosidase activity was observed exclusive ly in arterial, venous, and visceral SMCs. SM22 alpha -deficient mice are v iable and fertile. Their blood pressure and heart rate do not differ signif icantly front their control SM22 alpha (+/-) and SM22 alpha (+/+) littermat es. The vasculature and SMC-containing tissues of SM22 alpha -deficient mic e develop normally and appear to be histologically and ultrastructurally si milar to those of their control littermates. Taken together, these data dem onstrate that SM22 alpha is not required for basal homeostatic functions me diated by vascular and visceral SMCs in the developing mouse. These data al so suggest that signaling pathways that regulate SMC specification and diff erentiation from local mesenchyme are activated earlier in the angiogenic p rogram than previously recognized.