Disruption of a retinal guanylyl cyclase gene leads to cone-specific dystrophy and paradoxical rod behavior

One of two orphan photoreceptor guanylyl cyclases that are highly conserved from fish to mammals, GC-E (or retGC1) was eliminated by gene disruption. Expression of the second retinal cyclase (GC-F) as well as the numbers and morphology of rods remained unchanged in GC-E null mice. However, rods isol ated from such mice, despite having a normal dark current, recovered from a light flash markedly faster. Unexpectedly, the a- and b-waves of electrore tinograms (ERG) from dark-adapted null mice were suppressed markedly. Cones , initially present in normal numbers in the retina, disappeared by 5 weeks , based on ERG and histology. Thus, the GC-E-deficient mouse defines a mode l for cone dystrophy, but it also demonstrates that morphologically normal rods display paradoxical behavior in their responses to light.