GENE MAPPING IN INHERITED MURINE INTERSTITIAL NEPHRITIS

间质性肾炎是所有形式肾炎的最终共同途径。 慢性肾功能衰竭。中央病理生理过程是一种 针对肾脏自身的破坏性免疫反应 肾小管间质。该项目的目标是确定 导致遗传性间质性肾炎的基因 易感鼠(肾脏疾病称为“kd”)。这种疾病是 常染色体隐性遗传型及其遗传 表型与人类疾病有相似之处，青少年 一些人争论的肾单位/髓质囊性疾病 对其表达有一种自身免疫成分。整体而言 用于识别该kd基因的策略将涉及到 位置克隆。黄瓜品种的初步连锁研究 回交后代已经将该基因放置在两个微卫星之间 小鼠10号染色体上的标记。为了进一步缩小临界 地区，更多的多态将通过遗传鉴定 定向代表性差异分析(GDRDA)。一个 人工重叠酵母的连续阵列(重叠群) 染色体(YAC)和细菌人工染色体(BAG)克隆 将会被建造。一旦重叠群被组装，并且 关键区域缩小，候选基因将通过 文库的筛选。Kd基因1的鉴定 而对其结构和功能的后续研究将 提供了一条重要而新颖的线索，揭示了 肾脏间质损伤。

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.