著者

TOSHIYUKI HASEYAMA TOSHIKI FUJITA FUJIKO HIRASAWA MIKAKO TSUKADA HIDEKI WAKUI ATSUSHI KOMATSUDA HIROSHI OHTANI AKIRA B. MIURA HIROKAZU IMAI AKIO KOIZUMI

出版者

Tohoku University Medical Press

雑誌

The Tohoku Journal of Experimental Medicine (ISSN:00408727)

巻号頁・発行日

vol.198, no.4, pp.233-244, 2002 (Released:2004-04-19)

参考文献数

26

被引用文献数

32 43

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The Akita mouse, which has a mutation (Cys96Tyr) in the insulin 2 gene (Ins2Akita), is a model for diabetes. The male Akita mouse has diabetes, while females develop mild diabetes. This study aimed to investigate renal complications in the Akita mouse model, which has been maintained in a heterozygous state Ins2Akita (+/−) with a C57BL/6 background (B6). Renal function (BUN, creatinine), serum IgA concentrations and histological changes in the kidneys were evaluated in diabetic and control mice in a B6 background. Five each of male and female mice per group (diabetes vs. control) were killed at 10, 20, 30 and 40 weeks of age. The influence of major histocompatibility antigens (MHC) on renal complications was tested using male diabetic mice in a C3H/He (C3H) background. When compared with controls, diabetic males, but not females, developed impaired renal function with elevation of serum IgA after 30 weeks of age. Diabetic glomerulosclerosis advanced with age in both sexes. Diffuse granular mesangial deposits of IgA were detected by immunofluorescence microscopy in diabetic males after 20 weeks. We tested whether the IgA-associated lesions were influenced by MHC using diabetic males in a C3H background. Similar degrees of diabetic glomerulosclerosis and glomerular IgA deposition were found in mice with C3H and B6 backgrounds. Akita mouse is a unique mouse model showing both mesangial sclerosis and IgA nephropathy.

著者

Shanika Nanayakkara STMLD Senevirathna Tilak Abeysekera Rohana Chandrajith Neelakanthi Ratnatunga EDL Gunarathne Junxia Yan Toshiaki Hitomi Eri Muso Toshiyuki Komiya Kouji H. Harada Wanyang Liu Hatasu Kobayashi Hiroko Okuda Hideyuki Sawatari Fumihiko Matsuda Ryo Yamada Takao Watanabe Hideki Miyataka Seiichiro Himeno Akio Koizumi

出版者

Japan Society for Occupational Health

雑誌

Journal of Occupational Health (ISSN:13419145)

巻号頁・発行日

pp.13-0172-OA, (Released:2013-12-18)

被引用文献数

91

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Objectives: Previous investigations on chronic kidney disease of unknown etiology characterized by tubulointerstitial damages (CKDu) in the North Central Region (NCR) of Sri Lanka have supported the involvement of social, environmental and genetic factors in its pathogenesis. Methods: We conducted a social-environmental-and-genetic epidemiology study on a male population in NCR to investigate the genetic and environmental contributors. We recruited 311 case-series patients and 504 control candidates. Of the 504 control candidates, 218 (43%) were eliminated because of the presence of hypertension, proteinuria, high HBA1c, high serum creatinine or high alpha-1 microglobulin in urine. Results and Discussion: None of 18 metals measured (µg/l) in urine, including Cd, As and Pb, showed significantly higher concentrations in cases compared with controls. As speciation results showed that 75-80% of total urinary As was in the form of arsenobetaine, which is non-toxic to humans. None of the metal concentrations in drinking water samples exceeded guideline values. A genome-wide association study (GWAS) was conducted to determine the genetic contributors. The GWAS yielded a genome-wide significant association with CKDu for a single nucleotide polymorphism (SNP; rs6066043; P=5.23×10-9 in quantitative trait locus analysis; P=3.73×10-8 in dichotomous analysis) in SLC13A3 (sodium-dependent dicarboxylate transporter member 3). The population attributable fraction and odds ratio for this SNP were 50% and 2.13. Genetic susceptibility was identified as the major risk factor for CKDu. However, 43% of the apparently healthy male population suffers from non-communicable diseases, suggesting their possible influence on CKDu progression.