Development of Spontaneous nephotic rats and Their Pathological characteristics

Research Project

Project/Area Number	59870017
Research Category	Grant-in-Aid for Developmental Scientific Research
Allocation Type	Single-year Grants
Research Field	Experimental pathology
Research Institution	Shimane Medical University
Principal Investigator	YAMORI Yukio Shimane Medical University, 医学部, 教授 (80025600)
Co-Investigator(Kenkyū-buntansha)	沢村誠島根医科大学, 医学部, 助手 (00187303) NARA Yasuo Shimane Medical University, 医学部, 助手 (80116417) HORIE Ryoichi Shimane Medical University, 医学部, 助教授 (60127529) KIHARA Masahiro Shimane Medical University
Project Period (FY)	1984 – 1986
Project Status	Completed (Fiscal Year 1986)
Budget Amount *help	¥6,900,000 (Direct Cost: ¥6,900,000) Fiscal Year 1986: ¥1,000,000 (Direct Cost: ¥1,000,000) Fiscal Year 1985: ¥2,400,000 (Direct Cost: ¥2,400,000) Fiscal Year 1984: ¥3,500,000 (Direct Cost: ¥3,500,000)
Keywords	Nephrosis / Proteinuria / Serum creatinine / Minimal change nephrosis / Steroid hormone / Stroke-prone SHR (SHRSP) / OM rats / 血清アルブミン / クレアチニン / コレステロール / 副腎皮質ホルモン
Research Abstract	Since there had been no appropriate rat models for naphrosis, we attempted to start selective inbreeding of OM rats with moderate proteinuria which were found among 30 inbred rat strains collected through National Institutes of Health, U.S.A. from different laboratories in the world. The OM rats, thus established develop a marked proteinuria early in life which is progressively advanced by ageing process up to the severe proteinuria over 200 mg/day. These rats show bilateral enlargement of kidneys which light microscopically show a slight proliferative change of mesangial cells of glomeruli and dilatation of proximal tubuli with hyaline cylinders, and electronmicroscopically are consistent with minor glomerular abnormalities in minimal change nephrotic syndrome. These models were further treated with steroid hormone (Predonisolon 3 mg/kg, p.o.) but proteinuria was attenuated only temporally and rather resistant in general. In order to establishe a model with nephrotic and hypertensive renal lesions, these OM strains were cross-bred with stroke-prone SHR (SHRSP) to obtain <F_1> hybrid with moderate proteinuria and mild hypertension. From the cross breeding among <F_1> , <F_2> offsprings were obtained and further the offspring of <F_2> segregate generation with moderate hypertension and a marked proteinuria has been bred. These selectively bred OM rats and SPOM rats obtained by cross breeding between OM and SHRSP are regarded as new models for "adult type steroid resistant minimal change nephrosis".