Deletion of Emc1 in photoreceptor cells causes retinal degeneration in mice.

The endoplasmic reticulum membrane protein complex (EMC) plays a critical role in the synthesis of multi-pass membrane proteins. Genetic studies indicated that mutations in EMC1 gene were associated with retinal degeneration diseases, however the role of EMC1 in photoreceptor has not been proved. Here, we show that Emc1 ablation in the photoreceptor cells of mice recapitulated the retinitis pigmentosa (RP) phenotypes, including an attenuated scotopic electroretinogram (ERG) response and the progressive degeneration of rod cells and cone cells. Histopathological examination of tissues from rod-specific Emc1 KO (RKO) mice revealed mislocalized rhodopsin and irregularly arranged cone cells at the age of 2 months. Further immunoblotting analysis revealed decreased levels of membrane proteins and ER chaperones in 1-month-old RKO retinae, and this led us to speculate that the loss of membrane proteins is the main cause of the degeneration of photoreceptors. EMC1 most likely regulated the membrane protein levels at an earlier step in the biosynthetic process before the proteins translocated into the ER. Our study demonstrates the essential roles of Emc1 in photoreceptor cells, and reveals the mechanism through which EMC1 mutations are linked to RP.