免疫球蛋白（Ig）A1分子铰链区半乳糖缺失是IgA肾病发病的关键环节，但具体机制不详。CRISPR/Cas9基因编辑技术实现对特定DNA片段的敲除，能够有效便捷地“编辑”任何基因。我们前期通过大样本人群分析发现参与细胞增殖相关的HECW1、IgA mRNA合成的ELL2及IgA组装分泌的FCRLA的SNP位点与IgA1分子半乳糖缺失(Gd-IgA1)密切相关，并且这些SNP位点能够影响所在基因的表达。本课题拟在前期研究的基础上，收集IgA肾病患者和正常人，采用ELISA方法测定IgA1半乳糖缺失，分析HECW1、ELL2及FCRLA表达与Gd-IgA1相关性，进一步采用基因编辑技术，探讨HECW1、ELL2及FCRLA对B细胞Gd-IgA1产生的调控作用，并进一步进行功能验证，分析其对B细胞增殖、IgA mRNA合成及IgA组装分泌的影响，从新的角度揭示IgA肾病IgA1半乳糖缺失的机制。

Galactose-deficient IgA1 (Gd-IgA1) was considered to be a key contributor to the development of IgA nephropathy. However specific genes underlying this disorder are yet not known. CRISPR/Cas9 gene engineering technical editor target a specific genomic region. Our precious work indicated that HECW1, ELL2 and FCRLA were associated with the level of Gd-IgA1 in IgA nephropathy and could alter abundance of gene transcripts. In the further study, we plan to collect IgA nephropathy patients and healthy controls of Chinese to investigate the effect of HECW1, ELL2 and FCRLA in the development of Gd-IgA1 by vivo and vitro test. What's more, we'll study whether abnormal HECW1, ELL2 and FCRLA expression could cause to B lymphocyte proliferation, excessive synthesis of IgA1 mRNA and increased IgA1 secretion, which lead to an increase in the number of synthetic IgA1 exceeded the glycosylation enzyme catalytic ability, resulting to the production of Gd-IgA1. So the further study will help us to verify the pathogenesis of Gd-IgA1 in IgA nephropathy.