Retinal Degeneration in Mice Lacking the γ Subunit of the Rod cGMP Phosphodiesterase

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Abstract
The retinal cyclic guanosine 3′,5′-monophosphate (cGMP) phosphodiesterase (PDE) is a key regulator of phototransduction in the vertebrate visual system. PDE consists of a catalytic core of α and β subunits associated with two inhibitory γ subunits. A gene-targeting approach was used to disrupt the mouse PDEγ gene. This mutation resulted in a rapid retinal degeneration resembling human retinitis pigmentosa. In homozygous mutant mice, reduced rather than increased PDE activity was apparent; the PDEαβ dimer was formed but lacked hydrolytic activity. Thus, the inhibitory γ subunit appears to be necessary for integrity of the photoreceptors and expression of PDE activity in vivo.