权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Identification of a susceptible gene for the development of nephritis, which locates near the D8 GOT128 marker in rat chromosome 8

鉴定出肾炎发生的易感基因，该基因位于大鼠第 8 号染色体 D8 GOT128 标记附近

基本信息

批准号：
18500331
负责人：
MORITA Hiroyuki
金额：
$ 2.43万
依托单位：
Showa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

Focal and segmental glomerulosclerosis (FSGS) is a frequent finding in the progression of chronic renal failure. We identified a FSGS susceptibility gene in the BUF/Mna rat, which locate on rat chromosome 13. In the [(BUF/Mna x WKY/NCrj)F1 x BUF/Mna] backcross rats, we found that there was a modifier gene on rat chromosome 8 and 9. The purpose of the present study is to identify the gene on rat chromosome 8. In the F2 backcross cohort, urinary protein excretion increased in those individuals who showed BUF/Mna homozygousity for the D8Mit5 and ACPH markers. Using the NCBI data base UniSTS site, DNA markers were picked up. Some of them showed length polymorphism between BUF/Mna and WKY/NCrj strains and were used in typing. The results of the typing, together with gene information obtained from Ensemble data base, led us construct a physical map that indicated a candidate region on rat chromosome 8 (81.6-86.6 Mb). There were 30 genes in the region. PCR direct sequencing was performed, and then coding sequence of these genes were determined in the BUF/Mna and WKY/NCrj strains. A point mutation, which results in leucine-prolin substitution, was found in interphotoreceptor matrix proteoglycan 1 (Impg1) gene. Specific antibodies were produced by the use of DNA synthesis method. However, the antibodies were not capable of staining rat tissues and organs. (Lama1 is a modifier gene candidate on rat chromosome 9. Immunohistochemical analysis clearly showed that Lamal is expressed in tubular basement membranes of the kidney.)

局灶性和节段性肾小球硬化（FSGS）是慢性肾衰竭进展过程中常见的现象。我们在BUF/Mna大鼠中鉴定出一个FSGS易感基因，该基因位于大鼠13号染色体上。在[(BUF/Mna x WKY/NCrj)F1 x BUF/Mna]回交大鼠中，我们发现在大鼠8号和9号染色体上存在一个修饰基因。本研究的目的是鉴定大鼠8号染色体上的基因。在F2回交队列中，在 D8Mit5 和 ACPH 标记显示 BUF/Mna 纯合性的个体中，尿蛋白排泄增加。使用 NCBI 数据库 UniSTS 站点，提取 DNA 标记。其中一些在BUF/Mna和WKY/NCrj菌株之间表现出长度多态性并用于分型。分型结果与从 Ensemble 数据库获得的基因信息一起构建了一个物理图谱，该图谱指示了大鼠 8 号染色体上的候选区域 (81.6-86.6 Mb)。该区域有30个基因。进行PCR直接测序，然后确定BUF/Mna和WKY/NCrj菌株中这些基因的编码序列。在光感受器间基质蛋白聚糖 1 (Impg1) 基因中发现了一个点突变，导致亮氨酸-脯氨酸取代。利用DNA合成方法产生特异性抗体。然而，这些抗体不能对大鼠组织和器官进行染色。（Lama1 是大鼠 9 号染色体上的候选修饰基因。免疫组织化学分析清楚地表明 Lamal 在肾小管基底膜中表达。）