Retinal degeneration in mice lacking the gamma subunit of the rod cGMP phosphodiesterase.
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 alpha and beta subunits associated with two inhibitory gamma subunits. A gene-targeting approach was used to disrupt the mouse PDEgamma 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 PDEalphabeta dimer was formed but lacked hydrolytic activity. Thus, the inhibitory gamma subunit appears to be necessary for integrity of the photoreceptors and expression of PDE activity in vivo.
Tsang
S H
SH
Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University, College of Physicians and Surgeons, New York 10032, USA.
Gouras
P
P
Yamashita
C K
CK
Kjeldbye
H
H
Fisher
J
J
Farber
D B
DB
Goff
S P
SP
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002678:Chimera; D003433:Crosses, Genetic; D006152:Cyclic GMP / Q000378:metabolism*; D004596:Electroretinography; D004789:Enzyme Activation; D005260:Female; D018390:Gene Targeting; D006801:Humans; D008027:Light; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D012160:Retina / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D012162:Retinal Degeneration / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D017948:Retinal Rod Photoreceptor Cells / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000473:pathology
D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006152:Cyclic GMP