Ceramidases are key enzymes in the regulation of the cellular levels of ceramide, sphingosine, and S1P.To explore the physiological functions of ceramidases, we disrupted the gene encoding neutral ceramidase (Asah2) in mice. Asah2 null mice have a normal life span and do not show obvious abnormalities or major alterations in total ceramide levels in tissues. The Asah2-encoded neutral ceramidase is highly expressed in the small intestine along the brush border, suggesting that the neutral ceramidase may be involved in a pathway for the digestion of dietary sphingolipids. Indeed, Asah2 null mice were deficient in the intestinal degradation of ceramide. Thus, the results indicate that the Asah2-encoded neutral ceramidase is a key enzyme for the catabolism of dietary sphingolipids and regulates the levels of bioactive sphingolipid metabolites in the intestinal tract. We are currently utilizing the Asah2 null mice to determine if defective catabolism of sphingolipids alters the growth of intestinal tumors.

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Project End
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Budget End
Support Year
7
Fiscal Year
2013
Total Cost
$599,767
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Kono, Mari; Tucker, Ana E; Tran, Jennifer et al. (2014) Sphingosine-1-phosphate receptor 1 reporter mice reveal receptor activation sites in vivo. J Clin Invest 124:2076-86
Olivera, Ana; Allende, Maria Laura; Proia, Richard L (2013) Shaping the landscape: metabolic regulation of S1P gradients. Biochim Biophys Acta 1831:193-202