Effect of a single nucleotide polymorphism of complement decay accelerating factor (DAF) on proteinuria in BUF/Mna rat

BUF/MNA株由于局灶性和节段性肾小球硬化(FSGS)而自发发展为蛋白尿。精细数量性状基因座(QTL)定位和同源性分析表明，DAF(Daf)的大鼠同源基因位于大鼠13号染色体蛋白尿易感基因座上，命名为PUL位点。BUF/MNA株Daf的编码序列(CSNP)在239位核苷酸位置存在C-T替代的单核苷酸多态性。在167只[BUF/MNA x WKYINCrj]F1×BUF/MNA大鼠中提取DNA。测定大鼠尿蛋白排泄量。然而，cSNP与尿蛋白排泄量之间的相关性分析在本项目期限内尚未完成。另一方面，将含有Daf的BUF/MNA株的PUL区转移到WKY/NCRJ株的遗传背景中，建立了一个同源株。取同系大鼠(n=7)和WKY/NCRJ大鼠(n=7)行单侧肾切除。3个月和9个月时，同源基因大鼠肾小球硬化评分显著高于WKY/NCRJ大鼠。3、6、9个月时，同源基因大鼠尿蛋白排泄量显著高于WKY/NCRJ大鼠。这些结果证实了含有Daf的PUL区对FSGS的发育具有生物学影响。

BUF/Mna strain spontaneously develops proteinuria due to focal and segmental glomeruloscierosis (FSGS). Fine quantitative trait locus (QTL) mapping and synteny analysis clarified that rat homologue of DAF (Daf) located on proteinuria susceptible locus, designated as Purl locus, of rat chromosome 13. A single nucleotide polymorphism in the coding sequence (cSNP) with C-T substitution was found at the nucleotide position 239 of the Daf cDNA in BUF/Mna strain. DNA was obtained in 167 [BUF/Mna x WKYINCrj] F1 x BUF/Mna rats. Urinary protein excretion of these rats were measured. However, analysis of correlation between cSNP and amount of urinary protein excretion has not been completed within the term of the present project. On the other hand, a congenic strain was established in which Purl region of BUF/Mna strain containing Daf was transferred to the genetic background of WKY/NCrj strain. Unilateral nephrectomy was performed in the congenic rats (N=7) and WKY/NCrj rats (N=7) used as controls. At 3 and 9 months, glomerulosclerosis score of the congenic rats was significantly greater than that of WKY/NCrj rats. At 3, 6, and 9 months, urinary protein excretion of the congenic rats was significantly greater than that of WKY/NCrj rats. These results confirmed that Purl region containing Daf had biologic impact on the development of FSGS.