The physiological effects of deleting the mouse SLC30A8 gene encoding zinc transporter-8 are influenced by gender and genetic background.
The physiological effects of deleting the mouse SLC30A8 gene encoding zinc transporter-8 are influenced by gender and genetic background.
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DOI：
10.1371/journal.pone.0040972
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
O'Brien RM
中科院分区：
文献类型：
--
作者：
Pound LD;Sarkar SA;Ustione A;Dadi PK;Shadoan MK;Lee CE;Walters JA;Shiota M;McGuinness OP;Jacobson DA;Piston DW;Hutton JC;Powell DR;O'Brien RM
SLC30A8基因编码胰岛特异性转运蛋白ZnT - 8，据推测该蛋白为胰岛素晶体形成提供锌。SLC30A8的一个多态性变体与2型糖尿病易感性的改变有关。几个研究小组已经检测了整体Slc30a8基因缺失的影响，但结果差异很大，可能是由于所研究小鼠的129SvEv/C57BL/6J混合遗传背景所致。因此，我们试图消除129SvEv特异性修饰基因的干扰作用。
在纯C57BL/6J遗传背景下检测了Slc30a8缺失的影响。
雄性C57BL/6J Slc30a8基因敲除（KO）小鼠空腹胰岛素水平正常，从分离的胰岛中葡萄糖刺激的胰岛素分泌（GSIS）也没有变化，这与雄性混合遗传背景Slc30a8基因敲除小鼠中这两个参数分别约50%和约35%的下降形成鲜明对比。这一观察结果表明129SvEv特异性修饰基因调节Slc30a8缺失的影响。相比之下，雌性C57BL/6J Slc30a8基因敲除小鼠空腹胰岛素水平降低（约20%），尽管这与空腹血糖（FBG）或从分离的胰岛中的GSIS变化无关。这一观察结果表明性别也调节Slc30a8缺失的影响，尽管对于胰岛素分泌受损为何不伴有空腹血糖升高的生理学解释尚不清楚。雄性和雌性C57BL/6J Slc30a8基因敲除小鼠均未显示葡萄糖耐量受损。
我们的数据表明，尽管胰岛锌含量显著降低，但ZnT - 8的缺失对小鼠生理没有实质性影响。
The SLC30A8 gene encodes the islet-specific transporter ZnT-8, which is hypothesized to provide zinc for insulin-crystal formation. A polymorphic variant in SLC30A8 is associated with altered susceptibility to type 2 diabetes. Several groups have examined the effect of global Slc30a8 gene deletion but the results have been highly variable, perhaps due to the mixed 129SvEv/C57BL/6J genetic background of the mice studied. We therefore sought to remove the conflicting effect of 129SvEv-specific modifier genes. The impact of Slc30a8 deletion was examined in the context of the pure C57BL/6J genetic background. Male C57BL/6J Slc30a8 knockout (KO) mice had normal fasting insulin levels and no change in glucose-stimulated insulin secretion (GSIS) from isolated islets in marked contrast to the ∼50% and ∼35% decrease, respectively, in both parameters observed in male mixed genetic background Slc30a8 KO mice. This observation suggests that 129SvEv-specific modifier genes modulate the impact of Slc30a8 deletion. In contrast, female C57BL/6J Slc30a8 KO mice had reduced (∼20%) fasting insulin levels, though this was not associated with a change in fasting blood glucose (FBG), or GSIS from isolated islets. This observation indicates that gender also modulates the impact of Slc30a8 deletion, though the physiological explanation as to why impaired insulin secretion is not accompanied by elevated FBG is unclear. Neither male nor female C57BL/6J Slc30a8 KO mice showed impaired glucose tolerance. Our data suggest that, despite a marked reduction in islet zinc content, the absence of ZnT-8 does not have a substantial impact on mouse physiology.
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DOI：
10.1042/bj20090530
发表时间：
2009-07-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Pound LD;Sarkar SA;Benninger RK;Wang Y;Suwanichkul A;Shadoan MK;Printz RL;Oeser JK;Lee CE;Piston DW;McGuinness OP;Hutton JC;Powell DR;O'Brien RM
通讯作者：
O'Brien RM
在四种常用的近交小鼠菌株中的体内葡萄糖代谢。
影响因子：
7.7
作者：
Berglund, Eric D.;Li, Candice Y.;Poffenberger, Greg;Ayala, Julio E.;Fueger, Patrick T.;Willis, Shannon E.;Jewell, Marybeth M.;Powers, Alvin C.;Wasserman, David H.
通讯作者：
Wasserman, David H.
影响因子：
3.2
作者：
Lemaire K;Chimienti F;Schuit F
通讯作者：
Schuit F
DOI：
10.1042/bj20101488
发表时间：
2011-01-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Pound LD;Hang Y;Sarkar SA;Wang Y;Milam LA;Oeser JK;Printz RL;Lee CE;Stein R;Hutton JC;O'Brien RM
通讯作者：
O'Brien RM
影响因子：
5.8
作者：
Lauenborg, Jeannet;Grarup, Niels;Hansen, Torben
通讯作者：
Hansen, Torben