SLC7A2是课题组最新发现的麻风易感基因，其通过转运L型精氨酸在巨噬细胞活化及杀伤胞内菌的过程中起重要作用。深度重测序显示SLC7A2编码区的rs13259978位点与麻风紧密相关，分析显示其可能会影响SLC7A2蛋白在细胞膜上的定位，课题组前期免疫组化及qPCR结果也证实了SLC7A2由麻风分枝杆菌感染诱导高表达，提示rs13259978可通过抑制巨噬细胞功能进而导致麻风发生，但具体机制尚不明确。课题组拟在此基础上，通过免疫组化，qPCR技术探索麻风与正常对照中SLC7A2基因表达情况，并利用细菌活力测定实验对rs13259978位点影响SLC7A2转运L型精氨酸进而抑制胞内菌杀伤的作用进行分析；同时获取SLC7A2基因敲除斑马鱼模型，通过接种海鱼分枝杆菌，深入研究SLC7A2基因在分枝杆菌感染时，对机体免疫应答的影响，以明确麻风发病分子机理，为疾病风险预测与干预等提供理论依据。

SLC7A2, encodes protein which essential for the activation of macrophage via transferring L-arginine into cell, has been identified as one of the susceptibility genes of leprosy. High-throughput re-sequencing has determined the rare variant rs13259978（D28H）was significantly associated with leprosy. Functional analysis showed that rs13259978（D28H）may impair membrane localization of this protein. Previous study of our group also confirmed SLC7A2 was upregulated by infection of Mycobacterium leprae. These results implied that rs13259978（D28H）may be involved in pathogenesis of leprosy via impairing the function of macrophage, but the exact mechanism remains unclear. In this study, the differential expression of SLC7A2 will be analyzed between leprosy cases and health controls by qPCR and immunostaining. Furthermore, other molecular experiments, such as immunofluorescent staining, L-arginine uptake study and intracellular bacterial survival assays will be conducted to clarify how the candidate causal variant affects the function of SLC7A2. The in vivo mechanism of candidate causal variant regarding to the phenotype analysis of the granuloma formation, macrophage function and relative genes expression will be explored in Zebrafish. This study will greatly advance the biological understanding of leprosy as well as other mycobacterial infectious diseases.