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致病性OTUD3突变可能导致性结肠炎由于屏障功能障碍
Rabina Giri1, Minyi Lee2, Graham W Magor3
1Faculty of Medicine, The University of Queensland, Woolloongabba, Queensland, Australia; Inflammatory Bowel Disease Group, Mater Research Institute - The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia.
OTUD3基因的罕见变异与性结肠炎 (UC) 的发病有关. OTUD3对于维持结肠上皮质屏障功能和预防结肠炎至关重要.
科学领域:
- 遗传学 是一个遗传学.
- 胃肠病学 胃肠病学
- 免疫学 免疫学 免疫学
背景情况:
- 常见的遗传因素在性结肠炎 (UC) 的发展中发挥的作用有限.
- 严重的UC家族病例可能涉及影响新路径的罕见遗传变异.
研究的目的:
- 调查罕见遗传变异在UC病变发生中的作用.
- 确定涉及UC的新基因和途径.
主要方法:
- 在一个具有UC的多代家庭中,整体外基因组测序.
- 产生和分析Otud3缺乏的小鼠模型 (构成性和肠特异性).
- 在人类组织和细胞系中评估OTUD3表达,以及对OTUD3变异的功能研究.
主要成果:
- 在小鼠中,Otud3缺乏导致结肠壁完整性受损,ER压力增加和自发性结肠炎.
- 在UC患者队列中,罕见的,有害的OTUD3变异被丰富.
- 在UC患者的结肠表皮中观察到OTUD3表达的减少.
结论:
- OTUD3对于维持结肠上皮质屏障功能至关重要.
- OTUD3 功能障碍有助于性结肠炎的发病.
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