Podolin P L, Denny P, Armitage N, Lord C J, Hill N J, Levy E R, Peterson L B, Todd J A, Wicker L S, Lyons P A
Department of Autoimmune Diseases Research, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
Mamm Genome. 1998 Apr;9(4):283-6. doi: 10.1007/s003359900749.
Multiple genes control the development of autoimmune diabetes both in humans and in the nonobese diabetic (NOD) strain of mouse. Previously, three insulin-dependent diabetes (Idd) genes, Idd3, Idd10, and Idd17, were localized to mouse Chromosome (Chr) 3. The B10- or B6-derived resistance alleles at Idd10 and Idd3 together provide the NOD mouse with nearly complete protection from diabetes. In the present study, the 10.2-cM region encoding Idd10 was defined further with newly developed congenic strains. A locus, located in the centromeric 2.1 cM of the 10.2 cM region, contributed to the Idd10 trait. However, this locus did not account for the full effect of Idd10, suggesting the presence of a second gene in the distal portion of the 10.2-cM region. This second gene is designated as Idd18 and is localized to a 5.1-cM region. The resolution of the originally defined Idd3 locus into at least four separate loci, Idd3, Idd10, Idd17, and Idd18, illustrates the complex polygenic nature of diabetes.
多种基因控制着人类和非肥胖糖尿病(NOD)小鼠品系中自身免疫性糖尿病的发展。此前,三个胰岛素依赖型糖尿病(Idd)基因,即Idd3、Idd10和Idd17,被定位到小鼠3号染色体(Chr)上。Idd10和Idd3处源自B10或B6的抗性等位基因共同为NOD小鼠提供了几乎完全的糖尿病保护。在本研究中,利用新开发的近交系进一步确定了编码Idd10的10.2厘摩区域。位于10.2厘摩区域着丝粒端2.1厘摩处的一个位点对Idd10性状有贡献。然而,该位点并未解释Idd10的全部效应,这表明在10.2厘摩区域的远端存在第二个基因。这个第二个基因被命名为Idd18,定位于一个5.1厘摩的区域。最初定义的Idd3位点解析为至少四个独立的位点,即Idd3、Idd10、Idd17和Idd18,这说明了糖尿病复杂的多基因性质。