Analysis of SM22α-Deficient Mice Reveals Unanticipated Insights into Smooth Muscle Cell Differentiation and Function

Abstract

SM22␣ 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␣, gene targeting was used to generate SM22␣-deficient (SM22 ؊/؊LacZ ) mice. The gene targeting strategy employed resulted in insertion of the bacterial lacZ reporter gene at the SM22␣ initiation codon, permitting precise analysis of the temporal and spatial pattern of SM22␣ 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 ␤-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, ␤-galactosidase activity was observed exclusively in arterial, venous, and visceral SMCs. SM22␣-deficient mice are viable and fertile. Their blood pressure and heart rate do not differ significantly from their control SM22␣؉/؊ and SM22␣ ؉/؉ littermates. The vasculature and SMC-containing tissues of SM22␣-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␣ 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.

A Critical Role for Vascular Smooth Muscle in Acute Glucocorticoid-Induced Hypertension

“…On Western blot analysis of GR protein from hearts of control and Sm-22 Creϩ GR loxP/loxP mouse pairs, we found that, if anything, heart GR was slightly increased and certainly not decreased in Sm-22 Creϩ GR loxP/loxP mice ( Figure 4B), suggesting that there was no significant GR deletion from cardiac myocytes in our KO mice. Consistent with this and previous studies, 15,16 we found no differences in heart rate between the two groups either before or after DEX administration ( Figure 5). Our data suggest a critical role of VSM GR on the acute hypertensive response to GC.…”

Pericytes resident in postnatal skeletal muscle differentiate into muscle fibres and generate satellite cells

“…8g), in agreement with their pericyte origin and smooth muscle fate. This was confirmed by staining with an antibody recognizing the cytoskeletal protein SM22α, a smooth muscle-specific marker 24 (Fig. 8h); very few clones (less than 1%) contained both MyHC + and SM22α + cells (Fig.…”

Transgelin is a marker of repopulating mesangial cells after injury and promotes their proliferation and migration

“…27 While the analysis of transgelin-deficient mice demonstrated no developmental or basal homeostatic functions of transgelin in smooth muscle cells, 27 further studies implicate a critical role under pathophysiological settings. 28 In hypercholesterolemic ApoE-deficient mice, the lack of transgelin resulted in increased atherosclerotic lesion area and a higher proportion of proliferating smooth muscle cell-derived plaque cells.…”