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J Biol Chem, Vol. 274, Issue 25, 17725-17732, June 18, 1999

Targeted Expression of SV40 Large T-antigen to Visceral Smooth Muscle Induces Proliferation of Contractile Smooth Muscle Cells and Results in Megacolon

From the Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis, Indiana 46202-5120

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.

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