Miyawaki S, Muso E, Takeuchi E, Matsushima H, Shibata Y, Sasayama S, Yoshida H
Research Laboratories, Nippon Shinyaku Co., Ltd., Kyoto, Minami-ku, Japan.
Nephron. 1997;76(2):201-7. doi: 10.1159/000190169.
An outbred mouse strain known as ddY has been reported to spontaneously develop, late in life, mesangioproliferative glomerulonephritis with a severe glomerular immunoglobulin A (IgA) deposition that mimics human IgA nephropathy. However, the incidence of the disease in this strain is not very high, probably due to its heterogeneous genetic background. Therefore, we attempted to isolate a strain with a high incidence and an early onset of the disease through selection for high serum IgA from the outbred ddY mice. The selection procedure was successful in increasing the serum IgA level of the selected line and proved effective both in increasing the incidence and in accelerating the onset of the disease. We propose to designate this line of mice 'HIGA', denoting a line with high serum IgA levels. More than half of the mice from the HIGA strain showed a moderate to severe glomerular IgA deposition as early as 25 weeks of age. The severe deposition observed was comparable to that occasionally seen in the original nonselected ddY strain after 40 weeks of age. Thus, we have succeeded in generating a mouse model of IgA nephropathy with a high incidence and an early onset of glomerular IgA deposition. Using light microscopy, progressive and marked mesangial matrix accumulation was shown to develop in HIGA mice. However, they showed only mild proteinuria (100-300 mg/dl) and did not show hematuria.
据报道，一种远交系小鼠品系ddY在生命后期会自发发展为系膜增生性肾小球肾炎，伴有严重的肾小球免疫球蛋白A（IgA）沉积，类似于人类IgA肾病。然而，该品系中这种疾病的发病率不是很高，可能是由于其遗传背景的异质性。因此，我们试图通过从远交ddY小鼠中选择高血清IgA来分离出一种发病率高且疾病发病早的品系。选择过程成功提高了所选品系的血清IgA水平，并证明在增加发病率和加速疾病发病方面均有效。我们建议将该小鼠品系命名为“HIGA”，表示血清IgA水平高的品系。来自HIGA品系的半数以上小鼠早在25周龄时就出现了中度至重度的肾小球IgA沉积。观察到的严重沉积与原始未选择的ddY品系在40周龄后偶尔出现的沉积相当。因此，我们成功建立了一种IgA肾病小鼠模型，其肾小球IgA沉积发病率高且发病早。通过光学显微镜观察，HIGA小鼠出现了进行性且明显的系膜基质积聚。然而，它们仅表现出轻度蛋白尿（100 - 300mg/dl），未出现血尿。
