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Molecular and Cellular Biology, February 2001, p. 1336-1344, Vol. 21, No. 4
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.2001.21.4.1336-1344.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Analysis of SM22alpha -Deficient Mice Reveals Unanticipated Insights into Smooth Muscle Cell Differentiation and Function

Janet C. L. Zhang,1 Steven Kim,2 Brian P. Helmke,3 William W. Yu,1 Kevin L. Du,1 Min Min Lu,1 Mark Strobeck,1 Qian-Chun Yu,4 and Michael S. Parmacek1,*

Departments of Medicine,1 Bioengineering,3 and Cell and Molecular Engineering,4 University of Pennsylvania, Philadelphia, Pennsylvania 19104, and Department of Medicine, University of Chicago, Chicago, Illinois 606372

Received 17 October 2000/Accepted 7 November 2000

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.

* Corresponding author. Mailing address: Department of Medicine, University of Pennsylvania, 91234 Founders Pavilion, 3400 Spruce St., Philadelphia, PA 19104-4283. Phone: (215) 662-3140. Fax: (215) 349-8017. E-mail: parmacek{at}mail.med.upenn.edu.

Molecular and Cellular Biology, February 2001, p. 1336-1344, Vol. 21, No. 4
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.2001.21.4.1336-1344.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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