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Deficiency in class III PI3-kinase confers postnatal lethality with IBD-like features in zebrafish
Deficiency in class III PI3-kinase confers postnatal lethality with IBD-like features in zebrafish
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Deficiency in class III PI3-kinase confers postnatal lethality with IBD-like features in zebrafish
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Deficiency in class III PI3-kinase confers postnatal lethality with IBD-like features in zebrafish
Deficiency in class III PI3-kinase confers postnatal lethality with IBD-like features in zebrafish

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Deficiency in class III PI3-kinase confers postnatal lethality with IBD-like features in zebrafish
Deficiency in class III PI3-kinase confers postnatal lethality with IBD-like features in zebrafish
Journal Article

Deficiency in class III PI3-kinase confers postnatal lethality with IBD-like features in zebrafish

2018
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Overview
The class III PI3-kinase (PIK3C3) is an enzyme responsible for the generation of phosphatidylinositol 3-phosphate (PI3P), a critical component of vesicular membrane. Here, we report that PIK3C3 deficiency in zebrafish results in intestinal injury and inflammation. In pik3c3 mutants, gut tube forms but fails to be maintained. Gene expression analysis reveals that barrier-function-related inflammatory bowel disease (IBD) susceptibility genes ( e-cadherin , hnf4a , ttc7a ) are suppressed, while inflammatory response genes are stimulated in the mutants. Histological analysis shows neutrophil infiltration into mutant intestinal epithelium and the clearance of gut microbiota. Yet, gut microorganisms appear dispensable as mutants cultured under germ-free condition have similar intestinal defects. Mechanistically, we show that PIK3C3 deficiency suppresses the formation of PI3P and disrupts the polarized distribution of cell-junction proteins in intestinal epithelial cells. These results not only reveal a role of PIK3C3 in gut homeostasis, but also provide a zebrafish IBD model. The functions of the class III PI3-kinase (PIK3C3) in gut homeostasis and innate immunity are poorly understood. Here the authors show that PIK3C3-deficient zebrafishes develop intestinal injury and inflammation due to mislocalization of cell junction proteins.