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 isolated from such mice, despite having a normal dark current, recovered from a light flash markedly faster. Unexpectedly, the a- and b-waves of electroretinograms (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 model for cone dystrophy, but it also demonstrates that morphologically normal rods display paradoxical behavior in their responses to light.
Yang
R B
RB
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9050, USA.
Robinson
S W
SW
Xiong
W H
WH
Yau
K W
KW
Birch
D G
DG
Garbers
D L
DL
D000221:Adaptation, Ocular; D000818:Animals; D003624:Darkness; D004596:Electroretinography; D005091:Exons; D006162:Guanylate Cyclase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D015183:Restriction Mapping; D012160:Retina / Q000201:enzymology*; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology / Q000502:physiology*; D017948:Retinal Rod Photoreceptor Cells / Q000473:pathology / Q000502:physiology*; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology
D006162:Guanylate Cyclase