RETINOPATHY INDUCED IN MICE BY TARGETED DISRUPTION OF THE RHODOPSIN GENE

Retinitis pigmentosa (RP) represents the most common mendelian degener ative retinopathy of man, involving death of rod photoreceptors, cone cell degeneration, retinal vessel attenuation and pigmentary deposits( 1,2). The patient experiences night blindness, usually followed by pro gressive loss of visual field. Genetic linkage between an autosomal do minant RP locus and rhodopsin(3), the photoreactive pigment of the rod cells, led to the identification of mutations within the rhodopsin ge ne in both dominant and recessive forms of Rp(3-7). To better understa nd the functional and structural role of rhodopsin in the normal retin a and in the pathogenesis of retinal disease, we generated mice carryi ng a targeted disruption of the rhodopsin gene. Rho(-/-) mice do not e laborate rod outer segments, losing their photoreceptors over 3 months . There is no rod ERG response in 8-week-old animals. Rho(+/-) animals retain the majority of their photoreceptors although the inner and ou ter segments of these cells display some structural disorganization, t he outer segments becoming shorter in older mice. These animals should provide a useful genetic background on which to express other mutant opsin transgenes, as well as a model to assess the therapeutic potenti al of re-introducing functional rhodopsin genes into degenerating reti nal tissues.