Epimorphin–/– mice have increased intestinal growth, decreased susceptibility to dextran sodium sulfate colitis, and impaired spermatogenesis
Yuan Wang, Lihua Wang, Hristo Iordanov, Elzbieta A. Swietlicki, Qun Zheng, Shujun Jiang, Yuzhu Tang, Marc S. Levin, Deborah C. Rubin
Yuan Wang, Lihua Wang, Hristo Iordanov, Elzbieta A. Swietlicki, Qun Zheng, Shujun Jiang, Yuzhu Tang, Marc S. Levin, Deborah C. Rubin
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Epimorphin–/– mice have increased intestinal growth, decreased susceptibility to dextran sodium sulfate colitis, and impaired spermatogenesis

Abstract

Dynamic and reciprocal epithelial-mesenchymal interactions are critical for the normal morphogenesis and maintenance of epithelia. Epimorphin has been identified as a unique molecule expressed by mesenchymal cells and myofibroblasts and has putative morphogenetic effects in multiple epithelial tissues, including intestine, skin, mammary gland, lung, gallbladder, and liver. To define the in vivo role of epimorphin, we created epimorphin-null mice by targeted inactivation of the epimorphin gene. Male epimorphin–/– mice are sterile due to abnormal testicular development and impaired spermatogenesis. Intestinal growth is increased in epimorphin–/– mice due to augmented crypt cell proliferation and crypt fission during the neonatal (suckling) period, mediated at least in part by changes in bone morphogenetic protein (Bmp) and Wnt/β-catenin signaling pathways. Colonic mucosal injury and colitis induced by dextran sodium sulfate (DSS) are ameliorated in epimorphin–/– mice, probably due to the increased proliferative capacity of the epimorphin–/– colon. These in vivo findings support the notion that epimorphin is a key stromal regulator of epithelial cell proliferation and growth in the intestine. In addition, our studies demonstrate a novel and critical role for epimorphin in regulating testicular development and growth as well as spermatogenesis.

Authors

Yuan Wang, Lihua Wang, Hristo Iordanov, Elzbieta A. Swietlicki, Qun Zheng, Shujun Jiang, Yuzhu Tang, Marc S. Levin, Deborah C. Rubin

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Figure 6

β-catenin expression in epimorphin–/– and WT mouse intestine.

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β-catenin expression in epimorphin–/– ...
Nuclear protein isolation was performed as described in Methods. (A) Representative immunoblots of intestinal nuclear protein from WT, epimorphin–/–, and epimorphin+/– (HET) mice. Nuclear proteins (20 μg per lane) were electrophoresed, and immunoblots were incubated with an anti–β-catenin antibody. Blots were sequentially probed with an anti-lamin B1 antibody to control for differences in loading. (B) Quantification of nuclear β-catenin expression normalized to lamin B1 expression.