Targeted expression of SV40 large T-antigen to visceral smooth muscle induces proliferation of contractile smooth muscle cells and results in megacolon.
Many pathological conditions result from the proliferation and de-differentiation of smooth muscle cells leading to impaired contractility of the muscle. Here we show that targeted expression of SV40 large T-antigen to visceral smooth muscle cells in vivo results in increased smooth muscle cell proliferation without de-differentiation or decreased contractility. These data suggest that the de-differentiation and proliferation of smooth muscle cells, seen in many pathological states, may be independently regulated. In the T-antigen transgenic mice the increased smooth muscle cell proliferation results in thickening of the distal colon. Consequently the distal colon becomes hyper-contractile and impedes the flow of digesta through the colon resulting in enlargement of the colon oral to the obstruction. These transgenic mice thus represent a novel model of megacolon that results from increased smooth muscle cell proliferation rather than altered neuronal innervation.
Herring
B P
BP
Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis, Indiana 46202-5120, USA. pherring@iupui.edu
Hoggatt
A M
AM
Smith
A F
AF
Gallagher
P J
PJ
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D003106:Colon / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D018390:Gene Targeting; D007150:Immunohistochemistry; D008531:Megacolon / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009119:Muscle Contraction / Q000235:genetics; D009124:Muscle Proteins / Q000235:genetics; D009130:Muscle, Smooth / Q000276:immunology / Q000378:metabolism*; D009219:Myosin-Light-Chain Kinase; D010446:Peptide Fragments; D010455:Peptides; D010641:Phenotype; D011401:Promoter Regions, Genetic
D000952:Antigens, Polyomavirus Transforming; D009124:Muscle Proteins; D010446:Peptide Fragments; D010455:Peptides; C060640:telokin; D009219:Myosin-Light-Chain Kinase