在转基因小鼠中诱导的胰岛素依赖性糖尿病是由II类MHC和干扰素-的异位表达引起的
N Sarvetnick1, D Liggitt, S L Pitts
1Department of Developmental Biology, Genentech, Inc., South San Francisco, California 94080.
Cell
|March 11, 1988
概括
转基因小鼠在胰腺β细胞中表达免疫基因,发生了自身免疫性糖尿病. 这导致了胰岛素生成细胞的破坏,突出显示了免疫分子表达在非免疫组织中的影响.
科学领域:
- 免疫学 免疫学 免疫学
- 内分泌学 在内分泌学.
- 遗传学 是一个遗传学.
背景情况:
- 胰腺产生胰岛素的β细胞对于葡萄糖平衡至关重要.
- 贝塔细胞的自身免疫破坏导致胰岛素依赖性糖尿病 (第一型糖尿病).
- 了解触发β细胞破坏的机制对于治疗开发至关重要.
研究的目的:
- 研究表达免疫效应分子在非免疫细胞,特别是胰腺β细胞中的后果.
- 为了确定免疫基因的向表达是否可以在转基因小鼠模型中诱导自身免疫糖尿病.
- 阐明主要基因相容性复合体II类和干扰素-在β细胞自身免疫中的作用.
主要方法:
- 在人类胰岛素促进体的控制下,生成表达II类主要基因相容性复合体 (MHC) 或干扰素-玛 (IFN-γ) 基因的转基因小鼠菌株.
- 在生成的小鼠模型中监测胰腺组织学和糖尿病的发展.
- 评估兰格兰斯小岛的完整性和炎症反应.
主要成果:
- 表达IA基因 (II类MHC分子) 两个链的转基因小鼠表现出兰格汉斯小岛的渐进性缩.
- 表达干扰素- (IFN-γ) 的小鼠表现出岛屿的炎症性破坏.
- 这两种模型都显示了胰岛素生成β细胞的消失,与胰岛素依赖性糖尿病的发展相吻合.
结论:
- 胰腺β细胞表达免疫效应分子,如II类MHC和IFN-γ,可以触发自身免疫破坏.
- 这些发现表明,非免疫细胞中特定免疫基因的表达与自身免疫性糖尿病的病变发生之间存在直接联系.
- 转基因模型为自身免疫糖尿病背后的机制提供了宝贵的见解,有助于开发向疗法.
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