PRPF31蛋白是剪接复合体的重要成分，在pre-mRNA的剪接过程中发挥作用。PRPF31突变可导致视网膜色素变性（RP），且存在外显不全的现象，但其突变引起RP的分子机制尚不明确。前期我们在世界上率先建立了prpf31敲除的斑马鱼模型，发现杂合子斑马鱼出现类似RP表型，而纯合子斑马鱼出现严重的视网膜发育缺陷。本项目将在此基础上进一步开展以下研究：明确prpf31杂合突变斑马鱼在不同时期的RP病理过程;分析prpf31突变是否在剪接水平上破坏光转导相关蛋白等的表达，利用RNA-seq技术发现prpf31在视网膜中新的靶基因,阐明其突变引起RP的分子机制,并分析prpf31完全敲除引起视网膜早期发育异常的原因;利用斑马鱼的数量优势探索prpf31突变的外显不全现象。我们的工作可为RP的诊断和治疗提供依据,还将为揭示PRPF31新的生理功能，阐明PRPF31突变引起RP的机制打下基础。

The protein encoded by PRPF31 is an important component of spliceosome, which plays a role in the splicing of pre-mRNA. Mutations in PRPF31 gene cause autosomal dominant retinitis pigmentosa (RP) with incomplete penetrance. The exact mechanism of how PRPF31 dysfunction leading to RP remains unclear. In this proposal, we generated the first prpf31 knockout zebrafish model with several kinds of mutant lines in the world. Our preliminary studies demonstrated that the heterozygotes show RP-like phenotypes, while the homozygotes show severe defects in retinal development. Based on these important findings, we are making further efforts to: (1) define the detailed disease course of RP in the prpf31 heterozygotes at different ages, and discover the roles of prpf31 in the regulation of retinal genes’ pre-mRNA splicing and expression by RNA-seq technique; (2) analyze the cause of abnormal early development of retina in prpf31 homozygotes. (3) explore the phenomenon of reduced penetrance of PRPF31 mutations taking the advantage of the large number of zebrafish. Our work will be help for diagnose and treatment of retinitis pigmentosa, and may reveal novel physiological functions of PRPF31 and the pathogenesis of PRPF31-associated RP.