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

Elisabeth André, François Conquet, Markus Steinmayr, Sharon C. Stratton, Vittorio Porciatti, Michael Becker-André

Research output: Contribution to journalArticle

149 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)3867-3877
Number of pages11
JournalEMBO Journal
Volume17
Issue number14
DOIs
StatePublished - Jul 15 1998

Keywords

  • Circadian
  • Fertility
  • Nuclear receptor
  • Retina
  • Spinal cord

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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