目的： 从Hedgehog(Hh)信号通路分析Adgrv1基因变异致Usher综合征(USH)的机制。

方法： 基于Adgrv1变异模型小鼠(Adgrv1^-/-)，野生型(WT)C57BL/6小鼠为对照，从细胞水平和视网膜组织水平采用qRT-PCR、HE、视网膜透射电镜和免疫荧光方法验证Adgrv1基因变异对纤毛结构的影响，分析Hh信号通路关键因子的表达变化。

结果：Adgrv1基因在视网膜和原代培养肺成纤维细胞中均有表达，但Adgrv1^-/-小鼠表达量显著降低。Adgrv1基因变异可造成光感受器外节盘膜溶解，以及原代肺成纤维细胞纤毛长度明显缩短，在视网膜组织和细胞水平Hh信号通路上Ptch1、Gli基因表达明显下降，而PKA基因表达上升。

结论：Adgrv1基因变异致视网膜色素变性，与Hh通路中PTCH1、GLI1蛋白表达降低，使得细胞纤毛缩短，视网膜光感受器细胞外节盘膜溶解有关。

METHODS: Based on Adgrv1 gene variant mice(Adgrv1^-/-), taking wild type(WT)C57BL/6 mice as controls, the expression of Adgrv1 gene and the structure of retina and cell cilia were analyzed by qRT-PCR, HE, transmission electron microscopy, and immunofluorescence. Additionally, the changes of key factors in the Hh signaling pathway caused by Adgrv1 gene variation were observed.

RESULTS: The Adgrv1 gene was expressed in both the retina and primary cultured lung fibroblasts of Adgrv1^-/- mice, but the expression levels were significantly decreased. The Adgrv1 gene variation can cause dissolution of the outer disc membrane of the retinal photoreceptors and significantly shorten the cilia length in primary lung fibroblasts. In the Hh signaling pathway, the expression of Ptch1 and Gli genes of Adgrv1^-/- was significantly reduced, while the expression of PKA genes was increased.

CONCLUSION:The Adgrv1 gene variation leads to shortened cell cilia and dissolution of the outer disc membrane of the retinal photoreceptors, resulting in retinitis pigmentosa, which is related to decreased expression of PTCH1 and GLI1 proteins in the Hh pathway.