title: Elevation of cGMP with normal expression and activity of rod cGMP-PDE in photoreceptor degenerate labrador retrievers.
abstract: Cyclic guanosine 3',5'-monophosphate (cGMP) levels were determined in retinas from a strain of Labrador Retrievers with inherited retinal dystrophy manifesting at early stages of retinal differentiation. The cGMP contents of dystrophic retinas of dogs from 1 to 4 months of age (n = 7) were significantly higher (p = 0.001) than in age-matched controls of the same breed (n = 11). Ultrastructure along the vertical retinal meridian was studied in developing retinas and findings were related to those of age-matched wild-type controls of the same breed. Slow central to peripheral progression of degeneration was observed in affected dogs. No differences were found in total cGMP-phosphodiesterase (PDE) activity, in PDE subunit composition as determined by Western blotting of 2-month-old homozygote affected retinas, or in the amino acid sequence deduced from the nucleotide sequence of the PDE beta-subunit as compared to controls. This model of photoreceptor degeneration thus is the first case of an apparent abnormality of cGMP metabolism that is not associated with a defect in the PDE catalytic subunits, and it is also the first reported model not associated with severe developmental abnormalities and rapid degeneration.
authors.affiliation: Department of Clinical Sciences/Surgery, Faculty of Veterinary Medicine, University of Helsinki, Finland.
authors.forename: B
authors.initials: B
authors.lastname: Kommonen
authors.forename: T
authors.initials: T
authors.lastname: Kylma
authors.forename: R J
authors.initials: RJ
authors.lastname: Cohen
authors.forename: J S
authors.initials: JS
authors.lastname: Penn
authors.forename: L
authors.initials: L
authors.lastname: Paulin
authors.forename: M
authors.initials: M
authors.lastname: Hurwitz
authors.forename: R L
authors.initials: RL
authors.lastname: Hurwitz
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D006152:Cyclic GMP / Q000378:metabolism*; D004195:Disease Models, Animal; D004283:Dog Diseases / Q000201:enzymology* / Q000473:pathology* / Q000503:physiopathology; D004285:Dogs; D004596:Electroretinography; D004789:Enzyme Activation; D008854:Microscopy, Electron; D009410:Nerve Degeneration; D010786:Photoreceptor Cells / Q000473:pathology; D012016:Reference Values; D012160:Retina / Q000378:metabolism / Q000648:ultrastructure; D017948:Retinal Rod Photoreceptor Cells / Q000201:enzymology*; D012174:Retinitis Pigmentosa / Q000201:enzymology / Q000473:pathology / Q000662:veterinary*; D014357:Trypsin / Q000494:pharmacology
chemical_list: D015106:3',5'-Cyclic-GMP Phosphodiesterases; D014357:Trypsin; D006152:Cyclic GMP