Acha-Orbea H, McDevitt H O
Proc Natl Acad Sci U S A. 1987 Apr;84(8):2435-9. doi: 10.1073/pnas.84.8.2435.
The nonobese diabetic mouse is recognized as an important animal model for human insulin-dependent diabetes mellitus. One of the components of susceptibility to this disease has been mapped to the major histocompatibility complex. In this study, full-length cDNA clones encoding the I-A alpha and beta chains from the nonobese diabetic mouse have been isolated and sequenced. They are identical to the sequences previously determined from the H-2d haplotype except for the sequence encoding the first external domain, the leader peptide, and the 5' untranslated region of the I-A beta chain molecule. Most strikingly, there are five consecutive nucleotide substitutions which lead to two radical amino acid changes in a region that is conserved between human and mouse. We suggest that the unique structure of the first external I-A beta chain domain is a major determinant in the disease susceptibility that maps to the major histocompatibility complex of the nonobese diabetic mouse.
非肥胖型糖尿病小鼠被公认为是人类胰岛素依赖型糖尿病的重要动物模型。对这种疾病易感性的一个组成部分已被定位到主要组织相容性复合体。在本研究中，已分离并测序了编码非肥胖型糖尿病小鼠I-Aα和β链的全长cDNA克隆。除了编码I-Aβ链分子的第一个外部结构域、前导肽和5'非翻译区的序列外，它们与先前从H-2d单倍型确定的序列相同。最引人注目的是，有五个连续的核苷酸替换，导致在人与小鼠之间保守的区域出现两个根本性的氨基酸变化。我们认为，I-Aβ链第一个外部结构域的独特结构是导致该疾病易感性的主要决定因素，该易感性与非肥胖型糖尿病小鼠的主要组织相容性复合体相关。
