突触蛋白II（SYN2）及其致病变异通过影响外周神经递质释放和脱髓鞘作用致麻风神经损害的机制研究

麻风分枝杆菌选择性侵犯外周神经，导致畸残的发生，但其嗜神经性和致神经损害的机制尚不明确。课题组既往发现的麻风易感基因-突触蛋白II（SYN2），是神经递质释放和神经结构形成的关键调节因子，这为麻风神经损害机制的研究提供了新的契机。本项目拟在前期研究的基础上，通过以下三个方面进行研究：1）SYN2在麻风中的表达模式分析及致病变异精细定位的研究；2）体外模型（In vitro）探讨SYN2在麻风分枝杆菌感染致外周神经脱髓鞘及神经损害的作用机制研究；3）麻风分枝杆菌感染CRISPER/CAS9构建的SYN2敲除斑马鱼致神经损害机制，以期理解SYN2基因在麻风分枝杆菌感染致神经损害发生机制中的作用，也为从根本上预防和控制麻风畸残危害提供理论依据。

Mycobacterium leprae could infect peripheral nerve and cause nerve damage in leprosy patients. However, the mechanism for infection and nerve damage is largely unknown. We have previously identified SYN2 as a susceptibility gene to leprosy, a key regulator of neurotransmitter release and nerve function, which may provide new opportunity to touch the mechanism for leprosy nerve damage. Based on our previous investigations, we aim to study the mechanisms of leprosy nerve damage through 1)The expression patterns of SYN2 and fine-mapping of its causal variants; 2) In vitro study the mechanisms of mycobacterium leprae causing peripheral nerve demyelination and damage; 3) In vivo study the mechanism of nerve damage through SYN2-knock out zebrafish model by CRISPER/CAS9. The project will benefit the understanding of functional role of SYN2 between mycobacterium leprae infection and nerve damage, which will also provide theoretic evidence for controlling and prevention the leprosy caused disability.