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.
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9050, USA.
R B
RB
Yang
S W
SW
Robinson
W H
WH
Xiong
K W
KW
Yau
D G
DG
Birch
D L
DL
Garbers
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