Lund T, Shaikh S, Kendall E, Campbell R D, Hattori M, Makino S, Cooke A
Department of Immunology, University College London Medical School, UK.
Diabetologia. 1993 Aug;36(8):727-33. doi: 10.1007/BF00401143.
The non-obese diabetic (NOD) mouse strain which spontaneously develops diabetes is a model for human Type 1 (insulin-dependent) diabetes mellitus. At least one of several genes controlling diabetes in the NOD mouse has been mapped to the MHC. Although previous experiments have implicated the MHC class II genes in the development of the disease, the existence of other MHC linked susceptibility genes has not been ruled out. In order to identify these susceptibility genes we have further characterized the MHC haplotype of the NOD mouse and two non-diabetic sister strains, the non-obese non-diabetic (NON) and cataract Shionogi (CTS). We have examined the mouse MHC class III region for the presence of homologous genes to 17 newly isolated human MHC class III region genes (G1, G2, G4, G6, G7a/valyl-tRNA synthetase, HSP70, G8, G9, G10, G12, G13, G14, G15, G16, G17 and G18). We detect unique hybridizing DNA fragments for 16 of the 17 genes in six inbred mouse strains (NOD, NON, CTS, B10, BALB/c and CBA/J) indicating that this part of the H-2 region is similar to the human MHC class III region. Using a panel of restriction enzymes we have defined RFLPs for 6 (G2, G6, HSP70, G12, G16, G18) of the 16 cross-hybridizing probes. The RFLPs demonstrate that NOD, NON and CTS mouse strains each have a distinct MHC haplotype in the MHC class III region.
非肥胖型糖尿病（NOD）小鼠品系会自发患上糖尿病，是人类1型（胰岛素依赖型）糖尿病的一种模型。控制NOD小鼠糖尿病的几个基因中至少有一个已被定位到主要组织相容性复合体（MHC）。尽管先前的实验表明MHC II类基因与该疾病的发生有关，但并未排除其他与MHC连锁的易感基因的存在。为了鉴定这些易感基因，我们进一步对NOD小鼠以及两个非糖尿病姐妹品系——非肥胖非糖尿病（NON）和白内障柴田（CTS）小鼠的MHC单倍型进行了特征分析。我们检查了小鼠MHC III类区域，以寻找与17个新分离的人类MHC III类区域基因（G1、G2、G4、G6、G7a/缬氨酰 - tRNA合成酶、热休克蛋白70、G8、G9、G10、G12、G13、G14、G15、G16、G17和G1'）同源的基因。我们在六个近交小鼠品系（NOD、NON、CTS、B10、BALB/c和CBA/J）中检测到了17个基因中的16个具有独特的杂交DNA片段，这表明H - 2区域的这一部分与人类MHC III类区域相似。使用一组限制性内切酶，我们为16个交叉杂交探针中的6个（G2、G6、热休克蛋白70、G12、G16、G18）定义了限制性片段长度多态性（RFLP）。这些RFLP表明，NOD、NON和CTS小鼠品系在MHC III类区域各自具有独特的MHC单倍型。
