Abstract
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.
Highlights
Under many pathological conditions smooth muscle cells undergo phenotypic modulation in which they change from a contractile quiescent phenotype to a synthetic proliferative state
Diseases that result in partial obstruction of the gut, such as Hirschsprung’s disease, cause a marked smooth muscle cell hypertrophy in cells oral to the obstruction, leading to megacolon
Hypertrophy of the gut following partial obstruction is accompanied by a large increase in the circumference of the intestine oral to the obstruction; this results from increased smooth muscle cell proliferation, in addition to cellular hypertrophy [23]
Summary
Transgenic Mice—The telokin promoter T2.4-SV40 large T-antigen and T310-SV40 large T-antigen mice were described previously [4, 24]. Transgenic mice were generated in C3HeB/FeQ inbred embryos by the Indiana University Transgenic Mouse Facility using standard protocols. Western and Northern Blotting—Western and Northern blots were performed as described previously [4, 25, 26]. Immunohistochemical Staining—Tissues were collected from transgenic mice, cryoprotected in 20% sucrose, phosphate-buffered saline, overnight. Cryoprotected tissues were embedded in tissue-freezing me-. The phenotypes of founder animals in which smooth muscle-specific expression of SV40 large T-antigen driven by either 2.4-kilobase pair (Telokin 2.4 T-Antigen) or 310-base pair (Telokin 310 T-antigen) fragments of the telokin promoter are shown
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
