A novel mutant gene inhibiting the progression of autoimmune glomerulonephritis

抑制自身免疫性肾小球肾炎进展的新型突变基因

• 批准号: 14370077
• 负责人: NOSE Masato
• 金额: $ 7.68万
• 依托单位: Ehime University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370077/
• 关键词: crescentic glomerulonephritis; coat color; linkage analysis; susceptibility loci; mutant gene; platelet function; pathogenomics; EOD mice; リコンビナントタンパク質; シナモンタンパク質; 突然変異; 自己免疫性疾患; 糸球体腎炎; マイクロサテライト解析; 毛色変異; 分子遺伝病理学

Crescentic glomerulonephritis (CreGN) is a representative outcome of autoimmune glomerulopathy, morphologically characteristics of extracapillary proliferative lesions in renal Bowman's space. Its rapid progression for irreversible renal failureis is of clinical importance. We previously had reported the establishment of murine disease-model (named EOD strain), of which the mice die of CreGN by 3 month-old. Recently, among these EOD mice, we found a spontaneous mutant strain of mice that exhibited much longer life-span and improved CreGN. Comparative pathological study using wild-type disease and mutant healthy mice demonstrated that a defect in platelet function was responsible for the improvement of CreGN. Furthermore, genetic analysis successfully identified the gene of mutation, which turned out to code a novel protein. Protein analysis showed that this mutation caused a loss of expression of this protein. The present study put forth an idea for therapeutic strategy against CreGN, that targets that molecular or a platelet function.

新月体肾小球肾炎（CreGN）是自身免疫性肾小球病的代表性结局，其形态学特征是肾Bowman间隙的毛细血管外增生性病变。其快速进展为不可逆性肾衰竭具有临床意义。我们以前曾报道过建立小鼠疾病模型（命名为EOD株），其中小鼠在3月龄时死于CreGN。最近，在这些EOD小鼠中，我们发现了一种自发突变的小鼠品系，表现出更长的寿命和改善的CreGN。使用野生型疾病和突变健康小鼠的比较病理学研究表明，血小板功能的缺陷是CreGN改善的原因。此外，遗传分析成功地确定了突变基因，该基因编码一种新的蛋白质。蛋白质分析表明，该突变导致该蛋白质的表达缺失。本研究提出了针对CreGN的治疗策略的想法，该策略针对该分子或血小板功能。

项目成果

能勢眞人: "膠原病モデルマウス -ゲノム病理学の視点から-"病理と臨床. 20・4. 399-406 (2002)

Masato Nose：“胶原病的小鼠模型——从基因组病理学的角度”病理学和临床研究20・4（2002）。

伊藤美津子, 態勢眞人(分担執筆): "別冊医学のあゆみ 腎疾患 -State of arts 2003-2005"医歯薬出版(株)(東京). 442 (2003)

伊藤光子、Suise 正人（合著者）：“Bessatsu 医学史：肾脏疾病 - 2003-2005 年艺术现状”石药出版有限公司（东京）442（2003 年）。

Murata, K., Nose, M., Ishii, N.et al.: "Constitutive OX40/OX40 ligand interaction induces autoimmune-like diseases."The Journal of Immunology. 169・8. 4628-4636 (2002)

Murata, K.、Nose, M.、Ishii, N.等人：“组成型 OX40/OX40 配体相互作用诱导自身免疫样疾病”。《免疫学杂志》169・8 (2002)。

Takahashi, S., Araki, K., Araki, M., Ito, M.R., Nakatani, K., Fujii, H., Izui, S., Vassalli, P., Nose, M.: "Suppression of experimental lupus nephritis by aberrant expression of the solublu E-selectin gene."Pathol Int. 52(3). 175-180 (2002)

Takahashi, S.、Araki, K.、Araki, M.、Ito, M.R.、Nakatani, K.、Fujii, H.、Izui, S.、Vassalli, P.、Nose, M.：“实验性狼疮肾炎的抑制

Murata, K., Nose, M., Ndhlovu, L.C., Sato, T., Sugamura, K., Ishii, N.: "Constitutive OX40/OX40 ligand interaction induces autoimmune-like diseases."J Immunol. 169(8). 4628-4636 (2002)

Murata, K.、Nose, M.、Ndhlovu, L.C.、Sato, T.、Sugamura, K.、Ishii, N.：“组成型 OX40/OX40 配体相互作用诱导自身免疫样疾病。”J 免疫学杂志。