Holowachuk E W, Greer M K, Martin D R
Banting and Best Department of Medical Research, C.H. Best Institute, University of Toronto, Ontario, Canada.
Nucleic Acids Res. 1987 Dec 23;15(24):10551-67. doi: 10.1093/nar/15.24.10551.
The major histocompatibility complex of the rat (RT1 complex) encodes two sets of class II molecules referred to as RT1.B and RT1.D. The complete structure of the RT1.D alpha u chain of the diabetes prone BB rat was determined by the isolation and characterization of a full size cDNA. Comparisons of the nucleotide and protein sequences of RT1.D alpha with the analogous molecules, H-2 I-E alpha and HLA DR alpha, revealed that these alpha chains have been highly conserved during evolution. Southern blot analysis indicated an association of the RT1 haplotypes, 'u' and 'l', with Bam H1 DNA bands of 9.8 kb and 11.7 kb, respectively. The BB rat develops insulin dependent diabetes as an autoimmune abnormality. Accumulating evidence suggests a cellular mediated etiology and the involvement of class II molecules. The steady state levels of RT1.D alpha mRNA were measured in splenic lymphocytes of diabetes prone BB rats and age matched histocompatible normal nondiabetic WF rats by a RNase protection assay. Compared to WF rats, elevated transcripts of RT1.D alpha were found in lymphocytes of young BB rats (approximately 4x and approximately 2.5x greater at 20-40 and 40-75 d, respectively). In lymphocytes of older diabetic and nondiabetic BB rats (greater than 75 d) the levels of RT1.D alpha mRNA were lower than in the young BB rats and were found at the WF control levels. The increased steady state RT1.D alpha mRNA levels in the young BB rats may reflect differences in the proportion of splenic lymphocytes expressing this gene (activated lymphocytes), and thus differences in splenic lymphocyte populations. The steady state RT1.D alpha mRNA levels in lymphocytes of the normal rats were found to be relatively similar at all ages examined. The increased class II gene transcripts found in lymphocytes of young BB rats indicates that they possess a highly activated immune system.
大鼠的主要组织相容性复合体（RT1复合体）编码两组II类分子，分别称为RT1.B和RT1.D。通过分离和鉴定全长cDNA，确定了糖尿病易感BB大鼠RT1.Dαu链的完整结构。将RT1.Dα的核苷酸和蛋白质序列与类似分子H-2 I-Eα和HLA DRα进行比较，发现这些α链在进化过程中高度保守。Southern印迹分析表明，RT1单倍型“u”和“l”分别与9.8 kb和11.7 kb的Bam H1 DNA条带相关。BB大鼠作为一种自身免疫异常会发展为胰岛素依赖型糖尿病。越来越多的证据表明其病因是细胞介导的，且涉及II类分子。通过核糖核酸酶保护试验，测定了糖尿病易感BB大鼠和年龄匹配的组织相容性正常非糖尿病WF大鼠脾淋巴细胞中RT1.DαmRNA的稳态水平。与WF大鼠相比，在年轻BB大鼠的淋巴细胞中发现RT1.Dα的转录本升高（在20 - 40天和40 - 75天时分别约高4倍和约2.5倍）。在老年糖尿病和非糖尿病BB大鼠（大于75天）的淋巴细胞中，RT1.DαmRNA水平低于年轻BB大鼠，且与WF对照水平相当。年轻BB大鼠中RT1.DαmRNA稳态水平的增加可能反映了表达该基因的脾淋巴细胞比例（活化淋巴细胞）的差异，从而反映了脾淋巴细胞群体的差异。在所有检测的年龄阶段，正常大鼠淋巴细胞中RT1.DαmRNA的稳态水平相对相似。在年轻BB大鼠淋巴细胞中发现的II类基因转录本增加表明它们拥有高度活化的免疫系统。
