First Department of Medicine, University Hospital Johannes-Gutenberg University Mainz, Mainz, Germany.
Rheumatol Int. 2013 Mar;33(3):613-22. doi: 10.1007/s00296-012-2406-4. Epub 2012 Apr 6.
Different murine models have been used as basis for Proteinase 3 (PR3)-associated vasculitis models, but sufficient reproduction of the human clinical manifestation has failed to this date. As a reliable animal model is needed to further elucidate the pathological value of PR3-ANCA, we developed a PR3-humanized transgenic mouse model, in order to induce a glomerulonephritis. Our huPR3-transgenic mice were injected i.v. with our monoclonal antibodies, either unlabeled or directly labeled by fluorescein isothiocyanate. For a period of 5 days, proteinuria and erythrocyte count were measured with urine dip sticks. None of the mice exhibited proteinuria and/or an abnormal number of erythrocytes in the urine. Five days after antibody treatment, the mice were killed and different organs were fixed and immunohistochemically assessed. In the case of the kidney, we could detect a glomerulonephritis. Our study is able to show that although a direct renal target was given in transgenic human PR3 mice, no renal pathology was detectable. Multifactorial mechanisms for PR3-ANCA involvement in the development of Wegener's granulomatosis must be hypothesized.
不同的鼠类模型已被用作蛋白酶 3（PR3）相关血管炎模型的基础，但迄今为止，尚未成功复制人类临床表现。由于需要可靠的动物模型来进一步阐明 PR3-ANCA 的病理价值，我们开发了一种 PR3 人源化转基因小鼠模型，以诱导肾小球肾炎。我们的 huPR3 转基因小鼠通过静脉注射未标记或直接用异硫氰酸荧光素标记的单克隆抗体。在 5 天的时间里，使用尿试纸测量蛋白尿和红细胞计数。没有一只小鼠出现蛋白尿和/或尿液中红细胞数量异常。抗体治疗 5 天后，处死小鼠并固定不同器官进行免疫组织化学评估。在肾脏的情况下，我们可以检测到肾小球肾炎。我们的研究能够表明，尽管在转基因人 PR3 小鼠中直接针对肾脏靶标，但无法检测到肾脏病理学。必须假设 PR3-ANCA 在韦格纳肉芽肿发展中的多因素机制。
