GENE MAPPING IN INHERITED MURINE INTERSTITIAL NEPHRITIS

间质性肾炎是所有形式的肾小球疾病的最终共同途径。 慢性肾衰竭中央病理生理过程是一个 针对肾脏自身的破坏性免疫反应 tubuloacetylum。该项目的目标是确定 一种导致遗传性间质性肾炎的基因， 易感小鼠（对于肾病称为“kd”）。述疾病是 遗传为常染色体隐性基因型， 并且表现型与人类疾病有相似之处， 肾单位结核/髓质囊性疾病，有些人认为 有自身免疫成分参与其表达 整体 用于识别该kd基因的策略将涉及 定位克隆从2000年开始的初步连锁研究 回交后代将该基因置于两个微卫星之间 小鼠10号染色体上的标记。 为了进一步缩小 区域，将通过遗传学方法鉴定其他多态性。 直接代表性差异分析（GDRDA）。 一 重叠酵母人工合成的连续阵列（重叠群） 染色体（YAC）和细菌人工染色体（BAG）克隆 将被建造。 一旦重叠群组装完成， 关键区域缩小，候选基因将被识别， cDNA文库的筛选。kd基因1的鉴定 随后对其结构和功能的研究将 提供了一个重要的和新颖的线索， 肾间质损伤

Interstitial nephritis is the final common pathway to all forms of chronic renal failure. The central pathophysiologic process is a destructive immune reaction directed towards the kidney's own tubulointerstitium. The goal of this project is to identify the gene which causes an inherited form of interstitial nephritis in susceptible mice (termed "kd" for kidney disease). The disease is inherited as an autosomal recessive genotype and the inheritance and phenotype has similarities to a human disease, juvenile nephronophthisis/medullary cystic disease which some have argued has an auto immune component to its expression. The overall strategy used to identify this kd gene will be one that involves positional cloning. Preliminary linkage studies from breedings of backcross progeny has placed the gene between two microsatellite markers on mouse chromosome 10. To further narrow the critical region, additional polymorphisms will be identified by genetically directed representational difference analysis (GDRDA). A contiguous array (contig) of overlapping yeast artificial chromosome (YAC) and bacterial artificial chromosome (BAG) clones will be constructed. Once the contig has been assembled, and the critical region narrowed, candidate genes will be identified by screening of cDNA libraries. The identification of the kd gene 1 and subsequent research into its structure and function will provide an important and novel clue to the mechanism of interstitial injury in the kidney.