SPONTANEOUS GLOMERULAR IGA DEPOSITION IN DDY MICE - AN ANIMAL-MODEL OF IGA NEPHRITIS

SPONTANEOUS GLOMERULAR IGA DEPOSITION IN DDY MICE - AN ANIMAL-MODEL OF IGA NEPHRITIS
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DOI:
10.1038/ki.1985.76
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发表时间:
1985-01-01
影响因子:
19.6
通讯作者:
MIURA, AB
MIURA, AB
中科院分区:
医学1区
文献类型:
--
作者:
IMAI, H;NAKAMOTO, Y;MIURA, AB

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研究发现,1920年前从德国引进并在日本饲养的非近交系dd系小鼠的ddy小鼠在肾小球系膜自发形成以IgA为主的沉积。在这份报告中,给出了这些小鼠肾脏病理的详细自然病史。分别于6、10、16、24、28、40、59周龄处死动物,每组9~10只。分析膀胱尿液,测定血清免疫球蛋白,并对肾组织标本进行光镜、荧光和电子显微镜检查。28wk蛋白尿(+)~(++),59wk蛋白尿(++)~(+),血尿阴性。肾小球系膜细胞在16wk时开始出现增殖,随后发展为明确的增殖性肾小球肾炎。在59周时,肾小球系膜基质增加。免疫荧光显示28wk时肾小球内有(++)、IgM(+)~(++)、IgA(+)和C3(+)四种免疫球蛋白。40wk时开始以IgA为主,肾小球形态为:IgA(++)~(+),IgG(+)~(++),IgM(.+-)。至(+)和C3(+)至(++)。免疫球蛋白中多克隆的IgA和IgG2a在40wk时急剧升高,59wk时与6wk时相比,IgA增加850%,IgG2a增加280%,IgG1增加170%,IgG2b增加90%,IgM增加60%。未检测到抗核抗体。因此,至少在40周龄以后,ddy小鼠可以作为自发性IgA肾炎的新的动物模型。并对IgA的可能来源进行了讨论。
It was found that ddY mice derived from non-inbred dd-stock mice brought from Germany before 1920 and then raised in Japan developed spontaneously IgA dominant deposition in the glomerular mesangium. In this report a detailed natural history of the renal pathology of those mice is given. The animals were fed rodent laboratory chow and sacrificed in groups of 9 to 10 at 6, 10, 16, 24, 28, 40 and 59 wk of age. The bladder urine was analyzed, serum Ig were measured, and the kidney specimens were evaluated with light, fluorescent and EM. Proteinuria was (+) to (++) after 28 wk and (++) to (+++) at 59 wk with negative hematuria. Mesangial cell proliferation began to appear at 16 wk, then progressed to a definite proliferative glomerulonephritis. At 59 wk an additional increase of the mesangial matrix occurred. By immunofluorescence, there were IgG of (++), IgM (+) to (++), IgA (+) and C3 (+) in the glomeruli until 28 wk. However, IgA started to be dominant at 40 wk and the glomerular pattern was IgA (++) to (+++), IgG (+) to (++), IgM (.+-.) to (+) and C3 (+) to (++) at 59 wk. Polyclonal IgA and IgG2a among Ig steeply rose at 40 wk, and at 59 wk IgA increased by 850%, IgG2a by 280%, IgG1 by 170%, IgG2b by 90%, and IgM by 60%, as compared with their level at 6 wk. There was no anti-nuclear antibody. Thus, ddY mice, at least after the age of 40 wk, can be used as a new animal model for spontaneous IgA nephritis. The probable origin of IgA is also discussed.