Three recessive loci required for insulin-dependent diabetes in nonobese diabetic mice.
Three recessive loci required for insulin-dependent diabetes in nonobese diabetic mice.
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非肥胖糖尿病小鼠中胰岛素依赖性糖尿病所需的三个隐性基因座。
DOI：
10.1126/science.2885918
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Coleman,DL
中科院分区：
文献类型：
--
作者：
Prochazka,M;Leiter,EH;Serreze,DV;Coleman,DL
非肥胖糖尿病（NOD）小鼠对胰岛素依赖型糖尿病易感性的多基因基础已通过与相关近交系非肥胖正常（NON）小鼠的异交而建立。对第一和第二回交后代的分析表明，显性糖尿病的发展至少需要三个隐性基因。一个是Idd-1 s，与17号染色体上的H-2K位点紧密连锁;另一个是Idd-2s，位于9号染色体上的Thy-1/Alp-1簇附近。分离的第三个，Idd-3s，可以显示在第二次回交。Idd-1和Idd-2均不能单独确定为胰岛炎的控制位点，胰腺白细胞浸润在大多数无症状的BC 1小鼠中是常见的。F1和BC 1小鼠表现出异常高的百分比脾T淋巴细胞的NOD的特点，这表明显性遗传的这一特点。NOD小鼠糖尿病发生的多基因控制，其中一个隐性基因与主要组织相容性复合体是几个控制位点之一，表明类似的多基因相互作用是人类糖尿病的基础。
A polygenic basis for susceptibility to insulin-dependent diabetes in nonobese diabetic (NOD) mice has been established by outcross to a related inbred strain, nonobese normal (NON). Analysis of first and second backcross progeny has shown that at least three recessive genes are required for development of overt diabetes. One,Idd-1s, is tightly linked to the H-2K locus on chromosome 17; another,Idd-2s, is localized proximal to theThy-1/Alp-1cluster on chromosome 9. Segregation of a third,Idd-3s, could be shown in a second backcross. NeitherIdd-1snorIdd-2scould individually be identified as the locus controlling insulitis; leukocytic infiltrates in pancreas were common in most asymptomatic BC1 mice. Both F1 and BC1 mice exhibited the unusually high percentage of splenic T lymphocytes characteristic of NOD, suggesting dominant inheritance of this trait. The polygenic control of diabetogenesis in NOD mice, in which a recessive gene linked to the major histocompatibility complex is but one of several controlling loci, suggests that similar polygenic interactions underlie this type of diabetes in humans.