Epimorphin(-/-) mice have increased intestinal growth, decreased susceptibility to dextran sodium sulfate colitis, and impaired spermatogenesis.
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/beta-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.
Wang
Yuan
Y
Department of Medicine and Speciality Care Service Line, St. Louis VA Medical Center, St. Louis, Missouri, USA.
Wang
Lihua
L
Iordanov
Hristo
H
Swietlicki
Elzbieta A
EA
Zheng
Qun
Q
Jiang
Shujun
S
Tang
Yuzhu
Y
Levin
Marc S
MS
Rubin
Deborah C
DC
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D003092:Colitis / Q000139:chemically induced* / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity*; D005260:Female; D018390:Gene Targeting; D007202:Indicators and Reagents / Q000633:toxicity; D007422:Intestines / Q000166:cytology / Q000254:growth & development* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D009024:Morphogenesis; D013091:Spermatogenesis / Q000502:physiology*; D013737:Testis / Q000166:cytology / Q000473:pathology / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D019485:Bone Morphogenetic Proteins; C504582:Epim protein, mouse; D007202:Indicators and Reagents; D008562:Membrane Glycoproteins; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D051176:beta Catenin; D016264:Dextran Sulfate