Holowachuk E W, Greer M K
Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada.
Diabetes. 1989 Feb;38(2):267-71. doi: 10.2337/diab.38.2.267.
The BB rat spontaneously develops insulin-dependent diabetes mellitus (IDDM) as an autoimmune abnormality involving the class II molecules of the major histocompatibility complex (MHC). The rat MHC (RT1 complex) encodes two class II loci, RT1.B and RT1.D. The possibility that variant or unique class II MHC molecules may be associated with IDDM susceptibility was directly examined by determining the nucleotide sequences of class II mRNAs and/or cDNAs from the diabetes-prone (DP) BB rat, the diabetes-resistant (DR) BB rat, the normal histocompatible Wistar-Furth (WF) rat, and the Lewis rat. Sequence analysis indicates that the beta-chains of the RT1.B and RT1.D molecules of the u haplotype from DP-BB, DR-BB, and WF rats are identical but that they are different from other rat alleles and published mouse class II sequences. At the nucleotide level, the NH2-terminal domain of RT1.D beta of the BB and WF rats differs by a single silent nucleotide substitution. Comparisons with the sequences of the Lewis rat indicate hypervariable allelic differences and that the u and I haplotypes are remarkably similar. These findings establish that the class II molecules of the DP-BB rat are not variant or unique and that unaltered class II molecules of the u haplotype support the autoimmune response in the BB rat.
BB大鼠会自发发展为胰岛素依赖型糖尿病（IDDM），这是一种涉及主要组织相容性复合体（MHC）II类分子的自身免疫异常疾病。大鼠MHC（RT1复合体）编码两个II类基因座，即RT1.B和RT1.D。通过测定糖尿病易感性（DP）BB大鼠、糖尿病抗性（DR）BB大鼠、正常组织相容性的Wistar-Furth（WF）大鼠和Lewis大鼠的II类mRNA和/或cDNA的核苷酸序列，直接检验了变异或独特的II类MHC分子可能与IDDM易感性相关的可能性。序列分析表明，DP-BB、DR-BB和WF大鼠的u单倍型的RT1.B和RT1.D分子的β链是相同的，但与其他大鼠等位基因以及已发表的小鼠II类序列不同。在核苷酸水平上，BB大鼠和WF大鼠的RT1.Dβ的NH2末端结构域因一个沉默核苷酸替换而有所不同。与Lewis大鼠序列的比较表明存在高度可变的等位基因差异，并且u和I单倍型非常相似。这些发现表明，DP-BB大鼠的II类分子并非变异或独特的，并且u单倍型未改变的II类分子支持BB大鼠的自身免疫反应。
