The Slc5a6 gene expresses a plasma membrane protein involved in the transport of the water-soluble vitamin biotin; the transporter is commonly referred to as the sodium-dependent multivitamin transporter (SMVT) because it also transports pantothenic acid and lipoic acid. The relative contribution of the SMVT system toward carrier-mediated biotin uptake in the native intestine in vivo has not been established. We used a Cre/lox technology to generate an intestine-specific (conditional) SMVT knockout (KO) mouse model to address this issue. The KO mice exhibited absence of expression of SMVT in the intestine compared with sex-matched littermates as well as the expected normal SMVT expression in other tissues. About two-thirds of the KO mice died prematurely between the age of 6 and 10 wk. Growth retardation, decreased bone density, decreased bone length, and decreased biotin status were 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. In vivo (and in vitro) transport studies showed complete inhibition in carrier-mediated biotin uptake in the intestine of the KO mice compared with their control littermates. These studies provide the first in vivo confirmation in native intestine that SMVT is solely responsible for intestinal biotin uptake. These studies also provide evidence for a casual association between SMVT function and normal intestinal health.

译文

:Slc5a6基因表达参与水溶性维生素生物素运输的质膜蛋白;该转运蛋白通常也称为钠依赖性多种维生素转运蛋白(SMVT),因为它也可以转运泛酸和硫辛酸。 SMVT系统对体内天然肠道中载体介导的生物素摄取的相对贡献尚未确定。我们使用Cre / lox技术来生成特定于肠道的(条件性)SMVT敲除(KO)小鼠模型,以解决此问题。与性别匹配的同窝幼仔相比,KO小鼠在肠道中不存在SMVT表达,在其他组织中也表现出预期的正常SMVT表达。大约三分之二的KO小鼠在6至10周龄之间过早死亡。在KO小鼠中观察到生长迟缓,骨密度降低,骨长度降低和生物素状态降低。显微镜分析显示KO小鼠的小肠(绒毛缩短,发育不良)和盲肠(慢性活动性炎症,发育不良)的组织学异常。体内(和体外)转运研究表明,与对照组的同窝仔猪相比,KO小鼠肠道中的载体介导的生物素摄取被完全抑制。这些研究首次证实了天然肠中SMVT负责肠道生物素的摄取。这些研究还为SMVT功能与正常肠道健康之间的偶然关联提供了证据。

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