Targeted expression of SV40 large T-antigen to visceral smooth muscle induces proliferation of contractile smooth muscle cells and results megacolon

Many pathological conditions result from the proliferation and de-different iation of smooth muscle cells leading to impaired contractility of the musc le. Here we show that targeted expression of SV40 large T-antigen to viscer al smooth muscle cells in vivo results in increased smooth muscle cell prol iferation without de-differentiation or decreased contractility. These data suggest that the de-differentiation and proliferation of smooth muscle cel ls, seen in many pathological states, may be independently regulated. In th e T-antigen transgenic mice the increased smooth muscle cell proliferation results in thickening of the distal colon. Consequently the distal colon be comes hyper-contractile and impedes the flow of digesta through the colon r esulting in enlargement of the colon oral to the obstruction. These transge nic mice thus represent a novel model of megacolon that results from increa sed smooth muscle cell proliferation rather than altered neuronal innervati on.