Résumé :
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SRF regulates the expression of muscle genes and immediate early genes and plays a crucial role in the heart and the skeletal muscles. Here, we investigated the consequences of inactivating SRF in adult gastrointestinal smooth muscle cells (SMCs). SRF-floxed mice were crossed with SM-CreERT2(ki) mice expressing a tamoxifen-inducible recombinase in SMCs. The mutant mice developed severe dilation of the intestinal tract associated with food stasis in the lumen 13 days after tamoxifen treatment. Mutant mice displayed cachexia and died between days 13 and 22. The dilation was associated with a thinning of the muscularis propria and was also observed in the urinary bladder. Ex vivo colonic contraction was impaired in the mutant before the occurrence of the dilation phenotype. The expression of several genes, including those encoding smooth muscle actin, the heavy chain of smooth muscle myosin and smoothelin, was 60 to 70% lower in mutants than in controls, and mutants also had a lower F/G actin ratio. Conclusions: SRF plays a central role in maintaining visceral smooth muscle contractile function in adults. Mice with a SMC-specific SRF mutation develop a severe motility disorder resembling chronic intestinal pseudoobstruction induced by visceral myopathy in humans, and may be used as an inducible model of this disorder. The dilatation of the visceral organs is similar to the dilatation of the heart chambers when SRF is inactivated in the adult heart and suggests the existence of common pathological pathways in the cardiac and intestinal pumps.
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