*2.2. Phosphodiesterase 6 Genes*

Mutations in genes encoding for the subunits forming the rod specific cyclic guanosine monophosphate (cGMP) phosphodiesterase (PDE) holoenzyme cause about 36,000 cases of autosomal recessive RP worldwide in humans, leading to the early onset of night blindness and retinal degeneration [32].

The rod PDE heteromeric holoenzyme has a catalytic core made of PDE6A and PDE6B subunits combined with two inhibitory gamma subunits [33]. Mutation in the gene encoding the alpha subunit of cGMP-PDE (Pde6a) causes PRA in the Cardigan Welsh corgi dog [34,35] and is a model of RP43 in humans, which accounts for 3% to 4% of recessive RP in North America [36,37]. Mutations in the gene

encoding the beta subunit of cGMP-PDE (Pde6b) have been identified in a few dog breeds (see below), including the Irish setter dog [38], which is a model for RP40 in humans and represents about 3% to 5% of the recessive forms of RP [39,40]. Disease mechanisms for these canine models are detailed below.
