Yip1 domain family, member 6 (Yipf6) mutation induces spontaneous intestinal inflammation in mice.
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.
Department of Genetics, The Scripps Research Institute, La Jolla, CA 92037, USA.
Katharina
K
Brandl
Wataru
W
Tomisato
Xiaohong
X
Li
Christina
C
Neppl
Elaine
E
Pirie
Werner
W
Falk
Yu
Y
Xia
Eva Marie Y
EM
Moresco
Roberto
R
Baccala
Argyrios N
AN
Theofilopoulos
Bernd
B
Schnabl
Bruce
B
Beutler
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D005260:Female; D005786:Gene Expression Regulation; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D020397:Goblet Cells / Q000378:metabolism* / Q000648:ultrastructure; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007079:Ileitis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D019879:Paneth Cells / Q000378:metabolism* / Q000648:ultrastructure
D008565:Membrane Proteins; D016264:Dextran Sulfate