Degeneration of cone photoreceptors induced by expression of the Mas1 protooncogene

Although transgenic expression of oncogenes typically leads to tumorigenesi s, oncogene expression directed to the rod photoreceptors leads to cell dea th without tumor formation. To evaluate the cellular and functional changes induced in cone photoreceptors by an oncogene, the Mas1 protooncogene was targeted to the cones of transgenic mice by the human red/green opsin promo ter. Mas1 was chosen because of its exclusive expression in the nervous sys tem and its homology to opsin. The overall histologic appearance of the tra nsgenic retina was normal and retinal tumors were never observed. While rod -mediated electroretinograms were normal in all respects, cone-mediated res ponses were diminished in direct relationship to the level of transgene exp ression as determined by Northern blot analysis. Responses of UV- and green -sensitive cones were reduced equivalently, and Northern analysis and immun ocytochemistry indicated that cone photoreceptor densities were markedly di minished throughout transgenic retinas. These results indicate that oncogen e expression in cones induces cell death without tumor formation and suppor t the possibility that aberrant oncogene expression may underlie some forms of hereditary retinal diseases. The Mas1 transgenic mice may be useful in understanding the cone photoreceptor degeneration that occurs in cone dystr ophies and age-related macular degeneration and in evaluating potential the rapies for these disorders. (C) 2000 Academic Press.