Ikegami H, Kawaguchi Y, Ueda H, Fukuda M, Takakawa K, Fujioka Y, Fujisawa T, Uchida K, Ogihara T
Department of Geriatric Medicine, Osaka University Medical School, Japan.
Biochem Biophys Res Commun. 1993 Apr 30;192(2):677-82. doi: 10.1006/bbrc.1993.1468.
To localize and characterize the MHC-linked diabetogenic gene of the NOD mouse, we studied the class III region of the MHC in the NOD mouse and related strains. Hsp70, Bat5, Tnfa and Tnfb loci were studied by microsatellite polymorphism analysis and/or restriction mapping. The CTS mouse had the same allele as the NOD mouse at the Hsp70 locus, but different alleles at the Bat5, Tnfa and Tnfb loci from those of the NOD mouse. Our previous studies indicated that in the CTS mouse, class II MHC was the same as that of the NOD mouse, but that class I MHC was different at both K and D loci, and that CTS MHC was diabetogenic in the presence of NOD background genes. These data map major genetic susceptibility to type 1 diabetes to the segment flanked by class I K and class III Bat5 loci. Moreover, since the diabetogenic effect of the CTS MHC is weaker than that of the NOD MHC, these data suggest the presence of a second MHC-linked gene or gene complexes that modulate susceptibility to type 1 diabetes outside this segment.
为了定位和鉴定NOD小鼠中与MHC连锁的致糖尿病基因，我们研究了NOD小鼠及其相关品系的MHCⅢ类区域。通过微卫星多态性分析和/或限制性酶切图谱分析，对Hsp70、Bat5、Tnfa和Tnfb基因座进行了研究。CTS小鼠在Hsp70基因座上与NOD小鼠具有相同的等位基因，但在Bat5、Tnfa和Tnfb基因座上的等位基因与NOD小鼠不同。我们之前的研究表明，在CTS小鼠中，Ⅱ类MHC与NOD小鼠相同，但Ⅰ类MHC在K和D基因座上均不同，并且在存在NOD背景基因的情况下，CTS MHC具有致糖尿病性。这些数据将1型糖尿病的主要遗传易感性定位到了由Ⅰ类K和Ⅲ类Bat5基因座侧翼的片段上。此外，由于CTS MHC的致糖尿病作用比NOD MHC弱，这些数据表明在该片段之外存在第二个与MHC连锁的基因或基因复合体，它们调节对1型糖尿病的易感性。
