Investigation of pathogenesis of Fabry nephropathy in novel model mouse

2014 Fiscal Year Final Research Report

• Project/Area Number: 23390223
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Niigata University
• Principal Investigator: MARUYAMA Hiroki 新潟大学, 医歯(薬)学総合研究科, 特任教授 (10293218)
• Co-Investigator(Kenkyū-buntansha): ISHII Satoshi 大分大学, 医学部, 研究員 (00222935)
• Co-Investigator(Renkei-kenkyūsha): NISHIKAWA Yuji 旭川医科大学, 医学部, 教授 (90208166) ; NAKAZAWA Mikio 新潟大学, 医歯学系, 教授 (80143759) ; MATSUYAMA Kiyoji 札幌医科大学, 保健医療学部, 教授 (40209664)
• Research Collaborator: HARA Masanori 新潟県立吉田病院, 小児科, 部長
• Project Period (FY): 2011-04-01 – 2015-03-31
• Keywords: ファブリー病 / 多尿 / 尿細管障害 / 髄質外層内帯 / ヘンレ上行脚太い部ヘンレ上行脚太い部 / ウロモジュリン / NKCC2

Outline of Final Research Achievements

Fabry disease (FD) is an X-linked lysosomal storage disorder resulting from a deficiency in the activity of alpha-galactosidase A. This enzyme deficiency causes the systemic lysosomal accumulation of glycolipids, primarily globotriaosylceramide (Gb3), in the vascular endothelium and other tissues. Morbidity and mortality from FD, caused by renal failure, cardiac disease, and early-onset stroke. Glako mice lack significant kidney disease. We generated symptomatic mouse model (G3stg/Glako) by cross-breeding Glako mice with transgenic mice expressing human Gb3 synthase. Polyuria was the conspicuous manifestation. The vacuolation dominated in medullary thick ascending limb of Henle’s loop (TAL) and the fibrosis mainly appeared in around mTAL. Real-time RT-PCR, western blot and immunohistochemical analyses revealed that the expression of TAL specific proteins, uromodulin and N+-K+-2C- cotransporter, were significantly decreased. These caused salt-wasting polyuria in G3stg/Glako.

Free Research Field

腎臓内科