Fulminant jejuno-ileitis following ablation of enteric glia in adult transgenic mice
Fulminant jejuno-ileitis following ablation of enteric glia in adult transgenic mice
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DOI：
10.1016/s0092-8674(00)81571-8
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发表时间：
1998-04-17
期刊：
影响因子：
64.5
通讯作者：
Sofroniew, MV
中科院分区：
文献类型：
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作者：
Bush, TG;Savidge, TC;Sofroniew, MV
为了研究星形胶质细胞的作用，我们从基因上靶向它们的消融。转基因小鼠产生表达单纯疱疹病毒胸苷激酶从小鼠胶质细胞酸性蛋白（GFAP）启动子。在成年转基因小鼠中，用抗病毒剂更昔洛韦皮下治疗2周优先消融空肠和回肠中表达转基因的GFAP阳性胶质细胞，引起暴发性和致命性空回肠炎。这种病理学与细菌过度生长无关，其特征为髓过氧化物酶活性增加、肌间神经元中度变性和腔内出血。这些研究结果表明，肠神经胶质细胞在维持肠道的完整性中发挥着重要作用，并表明它们的丧失或功能障碍可能有助于炎症性肠病的细胞机制。
To investigate the roles of astroglial cells, we targeted their ablation genetically. Transgenic mice were generated expressing herpes simplex virus thymidine kinase from the mouse glial fibrillary acidic protein (GFAP) promoter. In adult transgenic mice, 2 weeks of subcutaneous treatment with the antiviral agent ganciclovir preferentially ablated transgene-expressing, GFAP-positive glia from the jejunum and ileum, causing a fulminating and fatal jejuno-ileitis. This pathology was independent of bacterial overgrowth and was characterized by increased myeloperoxidase activity, moderate degeneration of myenteric neurons, and intraluminal hemorrhage. These findings demonstrate that enteric glia play an essential role in maintaining the integrity of the bowel and suggest that their loss or dysfunction may contribute to the cellular mechanisms of inflammatory bowel disease.