ELEVATION OF CGMP WITH NORMAL EXPRESSION AND ACTIVITY OF ROD CGMP-PDEIN PHOTORECEPTOR DEGENERATE LABRADOR-RETRIEVERS

Cyclic guanosine 3',5'-monophosphate (cGMP) levels were determined in retinas from a strain of Labrador Retrievers with inherited retinal dy strophy manifesting at early stages of retinal differentiation. The cG MP 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 contro ls of the same breed (n = 11). Ultrastructure along the vertical retin al meridian was studied in developing retinas and findings were relate d to those of age-matched wild-type controls of the same breed. Slow c entral to peripheral progression of degeneration was observed in affec ted dogs. No differences were found in total cGMP-phosphodiesterase (P DE) activity, in PDE subunit composition as determined by Western blot ting of 2-month-old homozygote affected retinas, or in the amino acid sequence deduced from the nucleotide sequence of the PDE P-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.