AIM: To analyze the mechanism of Usher syndrome(USH)caused by Adgrv1 gene variation through the Hedgehog(Hh)signaling pathway.

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.