与神经发育障碍相关的TMPRSS7中功能变异的丧失会破坏突触功能
Weiliang Lu1,2, Shuyuan Li3, Songchang Chen1,4
1Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, No. 419 Fangxie Road, Huangpu District, Shanghai 200011, China.
在TMPRSS7基因的衰退变异被确定为神经发育障碍的原因. 这种基因对大脑发育至关重要,正如突触功能受损和淘汰赛小鼠的神经行为缺陷所示.
科学领域:
- 遗传学 遗传学 是一个
- 神经科学是一个神经科学.
- 分子生物学分子生物学
背景情况:
- 超过一半的神经发育障碍缺乏已知的分子原因.
- 中枢神经系统 (CNS) 形在一些家庭中是经常发生的.
- TMPRSS7编码为母质酶-3,一种参与细胞外信号传递的蛋白酶.
研究的目的:
- 确定中枢神经系统反复形的中国家庭中神经发育障碍的遗传原因.
- 研究TMPRSS7在神经发育中的功能.
- 探索TMPRSS7相关的神经发育缺陷背后的分子机制.
主要方法:
- 一个患有神经发育障碍的家庭的遗传分析.
- 在患者中TMPRSS7变异的功能性表征.
- 产生和分析Tmprss7淘汰赛小鼠模型.
- 在淘汰的小鼠中进行神经行为测试.
- 脑组织的多omics分析.
主要成果:
- 在受影响的胎儿中确定了TMPRSS7 (p.R479H和p.S685Kfs*26) 中的复合异质合体变体.
- 患者表现出受损的母质酶-3酶原合成和缺陷的蛋白酶分泌.
- 淘汰赛Tmprss7小鼠显示了大脑中突触结构和功能的失调.
- 淘汰赛小鼠表现出显著的神经行为缺陷,包括空间学习和社交互动受损.
- 多omics数据显示,淘汰赛小鼠的大脑中的突触信号通路被破坏.
结论:
- TMPRSS7是一种候选基因,对正常神经发育至关重要.
- 在TMPRSS7中存在的缺陷与中枢神经系统形的神经发育障碍有关.
- 马特里-3在突触发育和功能中起着至关重要的作用.
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