Disruption of retinoid-related orphan receptor β changes circadian behavior, causes retinal degeneration and leads to vacillans phenotype in mice

The orphan nuclear receptor ROR beta is expressed in areas of the central nervous system which are involved in the processing of sensory information, including spinal cord, thalamus and sensory cerebellar cortices, Additionally, ROR beta localizes to the three principal anatomical components of the mammalian timing system, the suprachiasmatic nuclei, the retina and the pineal gland. ROR beta mRNA levels oscillate in retina acid pineal gland with a circadian rhythm that persists in constant darkness, ROR beta(-/-) mice display a ducklike gait, transient male incapability to sexually reproduce, and a severely disorganized retina that suffers from postnatal degeneration. Consequently, adult ROR beta(-/-) mice are blind, yet their circadian activity rhythm is still entrained by light-dark cycles, Interestingly, under conditions of constant darkness, ROR beta(-/-) mice display an extended period of free-running rhythmicity, The overall behavioral phenotype of ROR beta(-/-) mice, together with the chromosomal localization of the ROR beta gene, suggests a close relationship to the spontaneous mouse mutation vacillans described > 40 years ago.