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在非洲人群中常见的PIEZO1基因导致红细胞脱水并减轻菌感染
Shang Ma1, Stuart Cahalan1, Gregory LaMonte2
1Howard Hughes Medical Institute, Department of Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Cell
|March 27, 2018
概括
遗传性红细胞脱水障碍可能会预防疟疾. 红细胞中的PIEZO1功能增长突变减少了小鼠中的Plasmodium感染和实验性脑疟疾.
科学领域:
- 遗传学
- 血液学
- 免疫学
背景情况:
- 遗传性细胞分裂会导致红细胞脱水和轻微的血液溶解.
- 红细胞脱水在体外可降低菌感染,但体外保护性尚不清楚.
- 获得功能的PIEZO1突变与遗传性细胞分裂有关.
研究的目的:
- 在体内研究红细胞脱水对抗疟疾的作用.
- 探索PIEZO1在遗传性细胞分裂和疟疾中的功能.
- 确定与疟疾抗性相关的PIEZO1遗传变异.
主要方法:
- 设计了一种遗传性细胞分裂的小鼠模型.
- 在小鼠模型中评估Plasmodium感染和实验性大脑疟疾.
- 在非洲人群中鉴定和分析了一种新的人类PIEZO1等位基因 (E756del).
主要成果:
- 遗传性细胞瘤的小鼠模型显示对实验性脑疟疾的抗性.
- 红细胞和T细胞中的PIEZO1对保护至关重要.
- 在30%的非洲人口中发现了一种新的功能增益PIEZO1等位基因 (E756del).
- 有E756del的红细胞表现出脱水和减少了体外Plasmodium感染.
结论:
- 由于PIEZO1功能增益突变导致的红细胞脱水,可以保护人体免受实验性脑疟疾的侵害.
- E756del PIEZO1等位基因的高频率表明它在人类群体的疟疾耐药性中起作用.
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