Functional Study Of Emc1 In Retinal Photoreceptors

Hereditary retinal disease is a group of blind eye diseases which is closely related to genetic factors and caused by retinal degeneration,and retinitis pigmentosa（RP）is a common type,which is a hereditary retinal disease in which rod cells are mainly involved,accompanying or following abnormal function of cone cell.The global prevalence of RP has risen to 1/5000-1/3000,and more than 100 disease-causing genes associated with RP have been identified.Endoplasmic reticulum membrane complex 1（EMC1）is the largest subunit of the endoplasmic reticulum membrane complex（EMC）.Early studies found that EMC was related to endoplasmic reticulum associated degeneration.Later,researchers found that EMC could affect the transport of multiple transmembrane proteins such as rhodopsin.It has also briefly reported in the literature that EMC1 could affect the formation of rhodopsin in Drosophila,and some pathogenic mutations of the EMC1 have also been found in RP patients.However,there is no research on the function and mechanism of EMC1 in mammalian retina.In this study,the Cre-loxP system was used to generate Emc1 cone-and rod-specific conditional knockout mouse models,so as to investigate the role of Emc1 in the maintenance of photoreceptor cell function,thus revealing the pathogenesis of this gene-related retinopathy.In this study,the Emc1 cone-and rod-specific conditional knockout mouse models were generated firstly.After verifying the knockout efficiency of mice,the effects of Emc1 deletion on photoreceptor cells and related molecular mechanisms were explored from the organizational,physiological and molecular levels through a variety of molecular biological experiments.The experimental results showed that Emc1 gene knockout in mouse cones resulted in abnormal opsin synthesis and rapid cone death.Emc1 gene knockout in mouse rods resulted in reduced retinal electrophysiological dark response and rod degeneration,reproducing RP phenotype.Finally,the experimental results showed that the decreased expression of retinal membrane proteins was the main cause of rod’s death in Emc1 conditional knockout mice.The loss of EMC1 may prevent the smooth translocation of the new peptide chain of membrane protein to the endoplasmic reticulum for correct folding and assembly,resulting in a decrease in the expression level of membrane protein.Therefore,Emc1 plays a fundamental role in maintaining the function of retina photoreceptor cells.This study provides a new research idea for the molecular mechanism study of retinal diseases caused by Emc1 mutation,which gives a new clue for the study of EMC subunits and brings a new animal model to RP disease research.