Specific knockout of the Slc5a6 gene in mouse intestine via Cre/lox technology leads to impairment in biotin (and pantothenic acid) absorption

Abstract

The Slc5a6 gene expresses the sodium‐dependent multivitamin transporter (SMVT), a membrane protein that transports the water‐soluble vitamin biotin, as well as pantothenic acid and lipoate. The contribution of SMVT toward total carrier‐mediated absorption of biotin in native intestine in vivo is not known, and thus, was examined using intestine‐specific SMVT knockout (KO) generated by a Cre/lox technology. KO mice showed lack of expression of SMVT in the intestine compared to sex‐matched littermates but showed normal expression in other tissues. Almost 2/3rd of the KO mice died prematurely (ages of 6 and 10 weeks). Growth retardation, decreased bone density, decreased bone length and decreased biotin status were all observed in the KO mice. Microscopic analysis showed histological abnormalities in the small bowel (shortened villi, dysplasia) and cecum (chronic active inflammation, dysplasia) of the KO mice; the colon showed similar changes to the cecum but to a less extend. In vivo uptake studies demonstrated complete inhibition in carrier‐mediated biotin uptake in the intestine of the KO mice. These studies provide the first in vivo confirmation in native intestine that SMVT is the sole carrier for biotin absorption. The studies also provide evidence for a casual association between functionality of the SMVT and normal intestinal health/homeostasis. [Supported by DVA and NIH, (DK58057 and DK56061)].