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葡萄糖转运蛋白8(GLUT8)对胚胎发育并非必需,但会影响海马神经发生和心脏功能。

GLUT8 is dispensable for embryonic development but influences hippocampal neurogenesis and heart function.

作者信息

Membrez Mathieu, Hummler Edith, Beermann Friedrich, Haefliger Jacques-Antoine, Savioz Rebecca, Pedrazzini Thierry, Thorens Bernard

机构信息

Institute of Physiology, University of Lausanne, Center for Integrative Genomics, Génopode Building, CH-1015 Lausanne, Switzerland.

出版信息

Mol Cell Biol. 2006 Jun;26(11):4268-76. doi: 10.1128/MCB.00081-06.

Abstract

GLUT8 is a glucose transporter isoform expressed at high levels in testis; at intermediate levels in the brain, including the hippocampus; and at lower levels in the heart and several other tissues. GLUT8 is located in an intracellular compartment and does not appear to translocate to the cell surface, except in blastocysts, where insulin has been reported to induce its surface expression. Here, we generated mice with inactivation of the glut8 gene. We showed that expression of GLUT8 was not required for normal embryonic development and that glut8-/- mice had normal postnatal development, glucose homeostasis, and response to mild stress. Adult glut8-/- mice showed increased proliferation of hippocampal cells but no defect in memory acquisition and retention. Absence of GLUT8 from the heart did not alter heart size and morphology but led to an increase in P-wave duration, which was not associated with abnormal Nav1.5 Na+ channel or connexin expression. Thus, absence of GLUT8 expression in the mouse caused complex but mild physiological alterations.

摘要

葡萄糖转运蛋白8(GLUT8)是一种在睾丸中高表达、在包括海马体在内的大脑中中等水平表达、在心脏和其他几种组织中低水平表达的葡萄糖转运异构体。GLUT8位于细胞内区室,除了在囊胚中,胰岛素据报道可诱导其在细胞表面表达外,它似乎不会转运到细胞表面。在此,我们构建了葡萄糖转运蛋白8(glut8)基因失活的小鼠。我们发现,GLUT8的表达对于正常胚胎发育并非必需,且glut8基因敲除小鼠出生后的发育、葡萄糖稳态及对轻度应激的反应均正常。成年glut8基因敲除小鼠海马体细胞增殖增加,但在记忆获取和保持方面没有缺陷。心脏中缺乏GLUT8并未改变心脏大小和形态,但导致P波时限增加,这与异常的Nav1.5钠通道或连接蛋白表达无关。因此,小鼠中缺乏GLUT8表达会引起复杂但轻微的生理改变。

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