Dlicl deficiency impairs ciliogenesis of photoreceptors by destabilizing dynein

Cytoplasmic dynein 1 is fundamentally important for transporting a variety of essential cargoes along microtu bules within eukaryotic cells. However, in mammals, few mutants are available for studying the effects of defects in dyneincontrolled processes in the context of the whole organism. Here, we deleted mouse Dlicl gene encoding DLICI, a subunit of the dynein complex. DlicF/ mice are viable, but display severe photoreceptor degeneration. Ab lation of Dlicl results in ectopic accumulation of outer segment （OS） proteins, and impairs OS growth and ciliogen esis of photoreceptors by interfering with Rabllvesicle trafficking and blocking efficient OS protein transport from Golgi to the basal body. Our studies show that Dlicl deficiency partially blocks vesicle export from endoplasmic re ticulum （ER）, but seems not to affect vesicle transport from the ER to Golgi. Further mechanistic study reveals that lack of Dlicl destabilizes dynein subunits and alters the normal subcellular distribution of dynein in photoreceptors, probably due to the impaired transport function of dynein. Our results demonstrate that Dlicl plays important roles in ciliogenesis and protein transport to the OS, and is required for photoreceptor development and survival. The Dlicl/ mice also provide a new mouse model to study human retinal degeneration.