Autoimmune glomerulonephritis induced in congenic mouse strain carrying telomeric region of chromosome 1 derived from MRL/MpJ
Autoimmune glomerulonephritis induced in congenic mouse strain carrying telomeric region of chromosome 1 derived from MRL/MpJ
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DOI：
10.14670/hh-23.411
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发表时间：
2008-04-01
影响因子：
2
通讯作者：
Kon, Yasuhiro
中科院分区：
文献类型：
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作者：
Ichii, Osamu;Konno, Akihiro;Kon, Yasuhiro
在狼疮易感小鼠中，包括BXSB、NZW和NZB品系，染色体1的端粒区（Chr.1）包含主要的肾小球肾炎易感基因座，如Bxs 3、Sle 1和Nba 2。为了评估MRL株（一种红斑狼疮模型）是否在Chr. 1上具有肾小球肾炎易感基因座，我们基于C57 BL/6背景创建了携带MRL/MpJ Chr. 1（82 - 100 cM）的B6. MRLc 1（82 - 100）同源小鼠，并研究了肾脏病理学。从6个月大开始，B6.MRLc1（82-100）表现出疾病的发作，例如由于CD 3或B220阳性细胞增殖而导致的脾肿大、肾小球损伤以及血清抗dsDNA抗体浓度增加，并且这些在女性中发生得更早、更严重。12月龄以上的B6.MRLc1（82-100）小鼠的肾小球损伤评分高于C57 BL/6甚至野生型MRL/MpJ。免疫组化和电镜显示B6.MRLc1（82-100）肾小球基底膜上有免疫复合物沉积。对于IgG 1阳性肾小球的百分比，B6.MRLc1（82-100）的值显著高于C57 BL/6。B6. MRLc 1（82100）的血清尿素氮和抗dsDNA抗体水平显著高于C57 BL/6。总之，B6.MRLc1（82-100）明显发展为自身免疫介导的肾小球肾炎，我们证明MRL Chr.1包含一个新的肾小球肾炎易感基因座。我们将该位点命名为Mag（MRL自身免疫性肾小球肾炎），它为狼疮性肾炎的遗传基础和发病机制提供了新的见解。
In lupus erythematosus-prone mice, including the BXSB, NZW and NZB strains, telomeric regions of chromosome 1 (Chr.1) contain major glomerulonephritis susceptibility loci such as Bxs3, Sle1, and Nba2. To assess whether strain MRL, a model for lupus erythematosus, had glomerulonephritis susceptibility loci on Chr.1, we created B6.MRLc1 (82-100) congenic mice carrying MRL/MpJ Chr.1 (82-100cM) based on the C57BL/6 background and investigated renal pathology. From 6 months of age, B6.MRLc1 (82-100) showed the onset of diseases such as splenomegaly due to proliferation of CD3-or B220-positive cells, glomerular damage, and an increased serum anti-dsDNA antibody concentration, and these were earlier and severer in females. The score for glomerular damage was higher in B6.MRLc1 (82-100) mice over 12 months old than in C57BL/6 or even in wild-type MRL/MpJ. Immune-complex depositions were demonstrated on glomerular basement membrane in B6.MRLc1 (82-100) by immunohistochemistry and electron microscopy. For the percentage of IgG1-positive glomeruli, B6.MRLc1 (82-100) had significantly higher values than C57BL/6. In evaluations of clinical parameters, serum levels of blood urea nitrogen and the anti-dsDNA antibody in B6.MRLc1 (82100) were significantly higher than those in C57BL/6. In conclusion, B6.MRLc1 (82-100) clearly developed autoimmune-mediated glomerulonephritis, and we demonstrated that MRL Chr.1 contained a novel glomerulonephritis susceptibility locus. We named this locus Mag (MRL autoimmune glomerulonephritis) and it provided new insights into the genetic basis and pathogenesis of lupus nephritis.