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

补体衰变加速因子（DAF）单核苷酸多态性对BUF/Mna大鼠蛋白尿的影响

• 批准号: 14571037
• 负责人: MORITA Hiroyuki
• 金额: $ 2.05万
• 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: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571037/
• 关键词: rat experimental nephrology; proteinuria; focal and segmental glomerulosclerosis; disease susceptible gene; QTL analysis; SNP; 疾患発症感受性遺伝子; 一塩基多型; ラット

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.

BUF/Mna菌株由于局灶性和节段性肾小球硬化（FSGS）而自发地发展蛋白尿。精细的数量性状基因座（QTL）定位和同线性分析表明，大鼠Daf基因位于大鼠13号染色体上的蛋白尿易感基因Purl位点。在BUF/Mna株中发现了Daf基因编码序列的单核苷酸多态性（cSNP），在第239位碱基处有C-T取代。在167只[BUF/Mna x WKYINCrj] F1 x BUF/Mna大鼠中获得DNA。测定各组大鼠尿蛋白排泄量。然而，cSNP与尿蛋白排泄量之间的相关性分析在本项目期间尚未完成。另一方面，将含有Daf的BUF/Mna株的Purl区转移到WKY/NCrj株的遗传背景中，建立了同源株。同系大鼠（N=7）行单侧肾切除术，WKY/NCrj大鼠（N=7）作为对照。在3个月和9个月时，同类大鼠的肾小球硬化评分显著大于WKY/NCrj大鼠。在3、6、9个月时，同系大鼠的尿蛋白排泄量显著大于WKY/NCrj大鼠。这些结果证实了含有Daf的Purl区域对FSGS的发展具有生物学影响。

项目成果

Rossi M, Morita H, et al.(2番目): "Heparan sulfate chains of perlecan are indispensable in the lens capsule but not in the kidney."EMBO J. 22. 236-245 (2003)

Rossi M, Morita H, et al. (2nd)：“基底膜聚糖的硫酸乙酰肝素链在晶状体囊中是不可或缺的，但在肾脏中则不然。”EMBO J. 22. 236-245 (2003)

Morita H at al.: "Collagenofibrotic glomerulopathy with a widespread expression of type-V collagen."Virchows Arch. 442. 163-168 (2003)

Morita H 等人：“胶原纤维化肾小球病，广泛表达 V 型胶原。”Virchows Arch。

Nakao, N, Yoshimura, A., Morita, H. et al.: "(3rd): Combination treatment of angiotensin-II receptor blocker and angiotensin-converting enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomized controlled trial."LANCET. 361. 117-124 (2003)

Nakao, N、Yoshimura, A.、Morita, H. 等人：“（第 3 版）：血管紧张素 II 受体阻滞剂和血管紧张素转换酶抑制剂联合治疗非糖尿病肾病 (COOPERATE)：一项随机对照试验

Suzuki, R., Morita, H.et al.: "(2nd): Mixed cryoglobulinemia due to chronic hepatitis C with severe pulmonary involvement."Internal Medicine. 42. 1210-1214 (2003)

Suzuki, R., Morita, H.et al.：“（第 2）：慢性丙型肝炎引起的混合性冷球蛋白血症，伴有严重的肺部受累。”内科。

Nakao N, Yoshimura A, Morita H et al.: "Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE) : a randomised controlled trial."Lancet. 361. 117-124 (2003)

Nakao N、Yoshimura A、Morita H 等人：“血管紧张素 II 受体阻滞剂和血管紧张素转换酶抑制剂联合治疗非糖尿病肾病 (COOPERATE)：一项随机对照试验。”《柳叶刀》。