Mutation in the auxiliary calcium-channel subunit CACNA2D4 causes autosomal recessive cone dystrophy.

Retinal signal transmission depends on the activity of high voltage-gated l-type calcium channels in photoreceptor ribbon synapses. We recently identified a truncating frameshift mutation in the Cacna2d4 gene in a spontaneous mouse mutant with profound loss of retinal signaling and an abnormal morphology of ribbon synapses in rods and cones. The Cacna2d4 gene encodes an l-type calcium-channel auxiliary subunit of the alpha (2) delta type.

Structural and functional abnormalities of retinal ribbon synapses due to Cacna2d4 mutation.

Purpose: In a spontaneous mutant substrain of C57BL/10 mice, severely affected retinal ribbon-type synapses have been described. The retinopathy was accompanied by a substantial loss in the activities of the second-order neurons. Rod photoreceptor responses were maintained with reduced amplitude, whereas cone activities were absent.