Mowat-Wilson综合征（MWS）是由转录因子Sip1突变引起的罕见遗传病，常见眼部缺陷有小眼，脉络膜，视网膜和虹膜缺损并伴有多种系统性异常。Sip1通过基因转录水平调控在早期神经系统发育，细胞凋亡，肿瘤转移等方面发挥功能，常与miRNA相互作用。我们前期研究表明Sip1敲除后，视网膜内核层细胞数量降低，但其对视觉功能影响尚不清楚。本项目拟研究Sip1对成年小鼠视觉功能影响，在Sip1视网膜特异性敲除小鼠上开展多层次研究：1）结构水平：眼底彩照，OCT，PRV病毒示踪检测视网膜结构，突触联系网络；2）功能水平：ERG检测整体视觉功能，fMRI鉴定视觉中枢活动，全细胞膜片钳技术鉴定神经节细胞兴奋性；3）分子水平：通过CHIP-seq和CLIP-seq鉴定Sip1作用下游DNA及上游调控miRNA。以此揭示MWS视觉功能损伤及Sip1参与调节分子机制，为视网膜发育和功能提供理论基础。

Mowat-Wilson syndrome （MWS） is a developmental genetic disorder associated with multiple anomalies including structural eye phenotypes such as microphthalmia, cataract and iris/retinal/optic disc coloboma. Mutations in the transcription factor SIP1 were found to cause MWS. It has been reported that Sip1 showed increases modulation of the stem-cell properties and the tumorigenic capacity. In the central neuron systems, Sip1 involved in cytogenesis of neuron and glial cells. The retina-specific ablation of Sip1 in mice caused significant loss of cells in the inner nuclear layer and gradual thinning of the retina. However, at present, it is unclear how Sip1 mutations cause visual information transduction abnormality with this syndrome. In this project, we plan to utilize a variety of experimental approaches including viral tracing, patch clamp recording, ERG recording, fMRI mapping, CHIP-seq and CLIP-seq to determine the role of Sip1 in retinal vision function; as well as the underlying regulatory network in which Sip1 participates. Our proposed studies are expected to not only unravel a novel mechanism underlying retinal signal transmission but also provide a useful framework for clinical diagnosis and therapy of MWS.