Retinopathy and attenuated circadian entrainment in Crx-deficient mice

Crx, an Otx-like homeobox gene, is expressed specifically in the photorecep tors of the retina and the pinealocytes of the pineal gland(1,2). Crx has b een proposed to have a role in the regulation of photoreceptor-specific gen es in the eye and of pineal-specific genes in the pineal gland. Mutations i n human CRX are associated with the retinal diseases, cone-rod dystrophy-2 (adCRD2; refs 3-5), retinitis pigmentosa(5) (RP) and Leber congenital amaur osis(5,6) (LCA), which all lead to loss of vision. We generated mice carryi ng a targeted disruption of Crx. Crx(-/-) mice do not elaborate photorecept or outer segments and lacked rod and cone activity as assayed by electroret inogram (ERG). Expression of several photoreceptor- and pineal-specific gen es was reduced in Crx mutants. Circadian entrainment was also affected in C rx(-/-) mice.