Susceptibility to streptozotocin-induced diabetes is mapped to mouse chromosome 11
Susceptibility to streptozotocin-induced diabetes is mapped to mouse chromosome 11
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DOI：
10.1016/j.bbrc.2004.12.149
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发表时间：
2005-03-04
影响因子：
3.1
通讯作者：
Ogihara, T
中科院分区：
文献类型：
--
作者：
Babaya, N;Ikegami, H;Ogihara, T
为了研究β细胞易感性对糖尿病易感性的贡献，我们在2型糖尿病动物模型NSY小鼠（STZ敏感的NOD小鼠的姐妹株）中研究了β细胞对单一高剂量STZ的易感性，并与STZ耐药的C3H小鼠进行了比较。发现NSY小鼠对STZ极为敏感。NSY小鼠在NOD小鼠中插入单个Chr11，将stz抗性C3H小鼠转化为stz敏感小鼠。在Chr11上发现了两个核苷酸替换的核氧还蛋白基因，这是stz诱导糖尿病的位置和功能候选基因。这些数据，再加上1型（Idd4）和2型（Niddln）易感基因在Chr11上的共定位，表明胰腺β细胞的内在易感性是由Chr11上的一个或多个基因决定的，这也可能导致自发性糖尿病的易感性。(C) 2005爱思唯尔公司版权所有。
To study the contribution of beta-cell vulnerability to susceptibility to diabetes, we studied beta-cell vulnerability to a single high dose of streptozotocin (STZ) in an animal model of type 2 diabetes, the NSY mouse, a sister strain of the STZ-sensitive NOD mouse, in comparison with the STZ-resistant C3H mouse. NSY mice were found to be extremely sensitive to STZ. Introgression of a single Chr11, where STZ-sensitivity was mapped in the NOD mouse, from NSY mice converted STZ-resistant C3H mice to STZ-sensitive. Two nucleotide substitutions were identified in the nucleoredoxin gene, a positional and functional candidate gene for STZ-induced diabetes on Chr11. These data, together with the co-localization of type 1 (Idd4) and type 2 (Niddln) susceptibility genes on Chr11, suggest that the intrinsic vulnerability of pancreatic beta cells is determined by a gene or genes on Chr11, which may also contribute to susceptibility to spontaneous diabetes. (C) 2005 Elsevier Inc. All rights reserved.