Analysis of SM22alpha-deficient mice reveals unanticipated insights into smooth muscle cell differentiation and function.
SM22alpha 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 SM22alpha, gene targeting was used to generate SM22alpha-deficient (SM22(-/-LacZ)) mice. The gene targeting strategy employed resulted in insertion of the bacterial lacZ reporter gene at the SM22alpha initiation codon, permitting precise analysis of the temporal and spatial pattern of SM22alpha 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. SM22alpha-deficient mice are viable and fertile. Their blood pressure and heart rate do not differ significantly from their control SM22alpha(+/-) and SM22alpha(+/+) littermates. The vasculature and SMC-containing tissues of SM22alpha-deficient mice develop normally and appear to be histologically and ultrastructurally similar to those of their control littermates. Taken together, these data demonstrate that SM22alpha 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.
Zhang
J C
JC
Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Kim
S
S
Helmke
B P
BP
Yu
W W
WW
Du
K L
KL
Lu
M M
MM
Strobeck
M
M
Yu
Q
Q
Parmacek
M S
MS
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D005314:Embryonic and Fetal Development / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D007763:Lac Operon; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D024510:Muscle Development; D009124:Muscle Proteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D009130:Muscle, Smooth / Q000166:cytology* / Q000254:growth & development / Q000502:physiology*; D015398:Signal Transduction; D015533:Transcriptional Activation
D008840:Microfilament Proteins; D009124:Muscle Proteins; C058992:Tagln protein, mouse; C051615:transgelin