神经髓鞘形成不良和先天性白内障（HCC）由Hyccin突变所致，但其病理机制和Hyccin蛋白功能还未知。我们发现果蝇Hyccin蛋白与膜蛋白RBO和胞浆蛋白PI4KIIIα形成复合体。下调Hyccin表达量导致在细胞上RBO和PI4KIIIα水平下降。敲减rbo、PI4KIIIα或Hyccin 都导致果蝇视觉通路中胶质细胞发育异常，光传导和运动等功能障碍。初步结果显示：在敲减Hyccin的细胞中表达自动上膜的mCD8-GFP-PI4KIIIα能部分修复上述障碍。以上结果暗示果蝇RBO、PI4KIIIα和Hyccin蛋白在同一个调控胶质细胞发育通路中起作用，且Hyccin的作用可能在上游。本课题拟构建HCC的果蝇和小鼠模型，明确Efr3/RBO和PI4KIIIα下调是否在Hyccin蛋白缺失引起的HCC中起介导作用，为HCC病理机制和诊治提供参考。

Hypomyelination and Congenital Cataract (HCC) is an autosomal recessive white mater disorder caused by Hyccin deficiency, but neither the mechanism of HCC nor the function of Hyccin protein is known. We found that Hyccin forms a complex with RBO/Efr3 and PI4KIIIα proteins, Hyccin deficiency decreases the levels of RBO and PI4KIIIα protein, and that knockdown of Hyccin, rbo andPI4KIIIα each produces a similar abnormal pattern of glia cell-formed network in the lamina, impairment of phototransduction and motor movement, and shortage of lifespan. Preliminary data shows expression of mCD8-GFP-PI4KIIIα rescued the above impairement. Those results suggest that Hyccin, RBO and PI4KIIIα function in a same pathway controlling glia development. This proposal is designed to establish fly and mouse models of HCC, and determine whether Hyccin deficiency-induced hypomyelination is mediated by down regulation of RBO and PI4KIIIα.