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Knockout mouse forms a great tool in identifying the perturbations in signaling networks. Retinal degeneration and signaling networks involved in it have long been an intriguing question. We ventured out in finding the networks by using rhodopsin kinase (Rhok) or arrestin (Sag) knockout and as well as both the knockouts in mice retina. Our screening analysis revealed that during initial exposure to light many apoptosis inducing transcription factors Hkep53, ATF4, c-FOS and GADD45 beta up-regulated but later phase of degeneration was accompanied by NF-kappaB and API expression.