FUNCTIONAL CONSEQUENCES OF ONCOGENE-INDUCED PHOTORECEPTOR DEGENERATION IN TRANSGENIC MICE

This study evaluated retinal function in mice following the expression of oncogenes under the control of photoreceptor-specific promoters in transgenic mice. Electroretinograms (ERGs) were recorded under stimul us conditions chosen to elicit rod- or cone-mediated components. In on e transgenic line (MOT1), the simian virus 40 large tumor antigen was expressed under the control of the mouse opsin promoter. MOT1 mice exh ibited an age-related decline in the amplitude of the rod-mediated ERG a-wave. In comparison, cone-mediated responses recorded from MOT1 mic e remained normal up to four months of age, the oldest age tested. In the second transgenic line (CMYC), the rat c-myc gene was expressed un der control of the human interphotoreceptor-retinoid binding protein p romoter. CMYC mice exhibited a rapid reduction of cone-mediated respon ses and a gradual loss of the rod ERG a-wave. Analysis of rod ERG a-wa ves obtained from young MOT1 and CMYC mice indicated that the rod ERG abnormalities reflect a reduction in the number of rods contributing t o the response with the retention of normal response properties in rod s that remain. These results support the possibility that aberrant exp ression of oncogenes may underlie some forms of human rod and cone-rod dystrophy.