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Publication : Smad3-null mice lack interstitial cells of Cajal in the colonic wall.

First Author  Vetuschi A Year  2006
Journal  Eur J Clin Invest Volume  36
Issue  1 Pages  41-8
PubMed ID  16403009 Mgi Jnum  J:135772
Mgi Id  MGI:3794455 Doi  10.1111/j.1365-2362.2006.01593.x
Citation  Vetuschi A, et al. (2006) Smad3-null mice lack interstitial cells of Cajal in the colonic wall. Eur J Clin Invest 36(1):41-8
abstractText  BACKGROUND: Transforming growth factor-beta (TGF-beta)/Smad's signalling pathway plays a pivotal role in organogenesis, oncogenesis, inflammation, repair and fibrosis. The aim of this study was to evaluate the morphology of muscle layers and the density and distribution of interstitial cells of Cajal (ICC) in the colon of Smad3 knockout mice. MATERIALS AND METHODS: Eighteen Smad3 wild-type mice and 12 null mice were sacrificed at age 4 months and the colons were collected for histology (Haematoxilin-Eosin, Masson thrichrome and Gomori silver staining), morphometry and immunohistochemistry (IHC) analysis. For IHC we used the c-Kit, alpha-smooth muscle actine (alpha-SMA), vimentin, desmin and neuronal cocktail (S-100, NSE, neurofilament 200) antibodies. RESULTS: When sacrificed, 40% of the null mice showed different degrees of colon dilatation when compared with the wild-type. Histological and morphometric evaluation revealed a significant reduction in muscle layer thickness of the colon in all the null mice when compared with the wild-type. Immunohistochemistry evaluation showed a marked reduction, or even absence, of c-Kit immunoreactivity, which identifies ICC, in the colon of all the null mice, compared with the wild-type. CONCLUSIONS: Smad3 null mice showed a marked reduction, or even absence, of ICC in the colon together with a concomitant reduction of intestinal smooth muscle layer thickness. This data could account for the colonic dilation observed in approximately 40% of the Smad3 null mice. Alteration of intestinal smooth muscle layers and ICC could also be involved in the resistance of the Smad3 null mice to develop colonic fibrosis.
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