THE 1ST EXTERNAL DOMAIN OF THE NONOBESE DIABETIC MOUSE CLASS-II I-A BETA-CHAIN IS UNIQUE
THE 1ST EXTERNAL DOMAIN OF THE NONOBESE DIABETIC MOUSE CLASS-II I-A BETA-CHAIN IS UNIQUE
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DOI：
10.1073/pnas.84.8.2435
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发表时间：
1987-04-01
影响因子：
11.1
通讯作者：
MCDEVITT, HO
中科院分区：
文献类型：
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作者：
ACHAORBEA, H;MCDEVITT, HO
非肥胖型糖尿病小鼠是研究人类胰岛素依赖型糖尿病的重要动物模型。对这种疾病的易感性的组成部分之一已被映射到主要组织相容性复合体。在本研究中，使用编码I-A α的全长cDNA克隆。和β来自非肥胖糖尿病小鼠的链已被分离并测序。除了编码第一个外部结构域、前导肽和I-A β的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。链状分子最引人注目的是，有五个连续的核苷酸取代，导致人类和小鼠之间保守的区域中的两个激进的氨基酸变化。我们认为，第一个外部I-A β的独特结构可能是由于其结构的不同而引起的。链结构域是疾病易感性的主要决定因素，其映射到非肥胖糖尿病小鼠的主要组织相容性复合体。
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.