Yokoi N, Kanazawa M, Kitada K, Tanaka A, Kanazawa Y, Suda S, Ito H, Serikawa T, Komeda K
Institute of Laboratory Animals, Faculty of Medicine, Kyoto University, Kyoto 606-01, Japan.
J Clin Invest. 1997 Oct 15;100(8):2015-21. doi: 10.1172/JCI119733.
The Long-Evans Tokushima Lean (LETL) rat, characterized by rapid onset of insulin-dependent (type I) diabetes mellitus (IDDM), no sex difference in the incidence of IDDM, autoimmune destruction of pancreatic beta cells, and no significant T cell lymphopenia, is a desirable animal model for human IDDM. We have established a diabetes-prone substrain of the LETL rat, named Komeda Diabetes-Prone (KDP) rat, showing a 100% development of moderate to severe insulitis within 220 d of age. The cumulative frequency of IDDM was 70% at 120 d of age, and reached 82% within 220 d of age. Here, we performed the first genome-wide scan for non-MHC IDDM susceptibility genes in this strain. The analysis of three crosses has led to the revelation of a major IDDM susceptibility gene, termed Iddm/kdp1, on rat chromosome (Chr) 11. Homozygosity for the KDP allele at this locus is shown to be essential for the development of moderate to severe insulitis and the onset of IDDM. Comparative mapping suggests that the homologues of Iddm/ kdp1 are located on human Chr 3 and mouse Chr 16 and would therefore be different from previously reported IDDM susceptibility genes.
长-伊文斯托库什马瘦型（LETL）大鼠的特征为胰岛素依赖型（I型）糖尿病（IDDM）发病迅速、IDDM发病率无性别差异、胰腺β细胞发生自身免疫性破坏且无明显的T细胞淋巴细胞减少，是一种适用于人类IDDM的理想动物模型。我们建立了LETL大鼠的糖尿病易患亚系，命名为小牧糖尿病易患（KDP）大鼠，其在220日龄内100%发生中度至重度胰岛炎。IDDM的累积发生率在120日龄时为70%，在220日龄内达到82%。在此，我们对该品系进行了首次全基因组扫描以寻找非MHC的IDDM易感基因。对三个杂交组合的分析揭示了大鼠11号染色体（Chr）上一个主要的IDDM易感基因，命名为Iddm/kdp1。该位点的KDP等位基因纯合性对于中度至重度胰岛炎的发展及IDDM的发病至关重要。比较图谱分析表明，Iddm/kdp1的同源基因位于人类3号染色体和小鼠16号染色体上，因此与先前报道的IDDM易感基因不同。
