糖尿病前期BB大鼠中肿瘤坏死因子（TNF）的异常产生与CD45R表达缺陷有关。

Abnormal TNF production in prediabetic BB rats is linked to defective CD45R expression.

作者信息

Rothe H, Schuller I, Richter G, Jongeneel C V, Kiesel U, Diamantstein T, Blankenstein T, Kolb H

机构信息

Diabetes Research Institute, Heinrich-Heine-University, Düsseldorf, Germany.

出版信息

Immunology. 1992 Sep;77(1):1-6.

PMID:1398757

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1421609/

Abstract

The genetic basis and diabetes association of aberrant tumour necrosis factor-alpha (TNF-alpha) production by activated peritoneal macrophages in diabetes-prone (dp) biobreeding (BB) rats was analysed. Southern blot analysis could not detect a restriction fragment length polymorphism for the TNF gene distinguishing dp BB rats from Wistar (Wi) rats and diabetes resistant (dr) BB rats. The contiguous genetic arrangement of lymphotoxin (LT) and TNF genes described in mouse and man was also found in the rat by cloning a chromosomal region covering both genes. In search of a polymorphic marker we amplified a (CA)n:(GT)n microsatellite in the TNF promoter region by polymerase chain reaction (PCR). We detected two alleles, (CA)26 and (CA)33, but no correlation with diabetes risk was seen. Crosses between dp BB rats and Wi or Lewis. 1A (Lew. 1A) rats, respectively, indicated that aberrant TNF-alpha production of activated macrophages is inherited dominantly with only weak penetrance. Analysis of the F2 generation and backcrosses with the two parental strains showed that aberrant TNF production co-segregates with lymphopaenia and defective CD45R expression, markers known to reflect a diabetes predisposing gene(s) outside the RT1 complex. We conclude that a single linkage group is responsible for both aberrant TNF production and defective T-cell maturation in dp BB rats.

摘要

分析了糖尿病倾向（dp）生物繁殖（BB）大鼠中活化腹膜巨噬细胞异常产生肿瘤坏死因子-α（TNF-α）的遗传基础及其与糖尿病的关联。Southern印迹分析未检测到TNF基因的限制性片段长度多态性，该多态性可区分dp BB大鼠与Wistar（Wi）大鼠以及糖尿病抗性（dr）BB大鼠。通过克隆覆盖淋巴毒素（LT）和TNF基因的染色体区域，在大鼠中也发现了在小鼠和人类中描述的LT和TNF基因的连续遗传排列。为了寻找多态性标记，我们通过聚合酶链反应（PCR）扩增了TNF启动子区域的（CA）n:（GT）n微卫星。我们检测到两个等位基因，（CA）26和（CA）33，但未发现与糖尿病风险相关。dp BB大鼠分别与Wi或Lewis. 1A（Lew. 1A）大鼠杂交，结果表明活化巨噬细胞异常产生TNF-α以显性方式遗传，且外显率较低。对F2代以及与两个亲本品系的回交分析表明，异常TNF产生与淋巴细胞减少和CD45R表达缺陷共分离，这些标记反映了RT1复合体之外的一个糖尿病易感基因。我们得出结论，一个单一的连锁群负责dp BB大鼠中异常TNF产生和T细胞成熟缺陷。