TY - JOUR
T1 - Yip1 domain family, member 6 (Yipf6) mutation induces spontaneous intestinal inflammation in mice
AU - Brandl, Katharina
AU - Tomisato, Wataru
AU - Li, Xiaohong
AU - Neppl, Christina
AU - Pirie, Elaine
AU - Falk, Werner
AU - Xia, Yu
AU - Moresco, Eva Marie Y
AU - Baccala, Roberto
AU - Theofilopoulos, Argyrios N.
AU - Schnabl, Bernd
AU - Beutler, Bruce
PY - 2012/7/31
Y1 - 2012/7/31
N2 - Using an environmentally sensitized genetic screen we identified mutations that cause inflammatory colitis in mice. The X-linked Klein-Zschocher (KLZ) mutation created a null allele of Yipf6, a member of a gene family believed to regulate vesicular transport in yeast, but without known functions in mammals. Yipf6 is a five transmembrane-spanning protein associated with Golgi compartments. Klein-Zschocher mutants were extremely sensitive to colitis induced by dextran sodium sulfate (DSS) and developed spontaneous ileitis and colitis after 16 mo of age in specific pathogen-free housing conditions. Electron microscopy, gene expression, and immunocytochemistry analyses provided evidence that impaired intestinal homeostasis stemmed from defective formation and secretion of large secretory granules from Paneth and goblet cells. These studies support a tissue- and organ-specific function for Yipf6 in the maintenance of intestinal homeostasis and implicate the orthologous human gene as a disease susceptibility locus.
AB - Using an environmentally sensitized genetic screen we identified mutations that cause inflammatory colitis in mice. The X-linked Klein-Zschocher (KLZ) mutation created a null allele of Yipf6, a member of a gene family believed to regulate vesicular transport in yeast, but without known functions in mammals. Yipf6 is a five transmembrane-spanning protein associated with Golgi compartments. Klein-Zschocher mutants were extremely sensitive to colitis induced by dextran sodium sulfate (DSS) and developed spontaneous ileitis and colitis after 16 mo of age in specific pathogen-free housing conditions. Electron microscopy, gene expression, and immunocytochemistry analyses provided evidence that impaired intestinal homeostasis stemmed from defective formation and secretion of large secretory granules from Paneth and goblet cells. These studies support a tissue- and organ-specific function for Yipf6 in the maintenance of intestinal homeostasis and implicate the orthologous human gene as a disease susceptibility locus.
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U2 - 10.1073/pnas.1210366109
DO - 10.1073/pnas.1210366109
M3 - Article
C2 - 22802641
AN - SCOPUS:84864506705
SN - 0027-8424
VL - 109
SP - 12650
EP - 12655
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 31
ER -