Enhanced endocrine response to novel environment stress and lack of corticosterone circadian rhythm in <i>staggerer</i> (<i>Rora sg/sg</i>) mutant mice

Abstract

The staggerer (Rora sg/sg) mutation is a deletion in the retinoid-related orphan receptor (RORalpha) gene that prevents translation of the ligand-binding domain (LBD), leading to the loss of RORalpha activity. RORalpha is a transcription factor that belongs to the nuclear receptor superfamily. In the brain, RORalpha is expressed in specific areas, including the cerebellum and suprachiasmatic nucleus (SCN). The homozygous Rora sg/sg mutant mouse, of which the most obvious phenotype is ataxia associated with cerebellar degeneration, also overproduces inflammatory cytokines. Here we compared the response to novelty stress of staggerer and wild-type mice as well as their diurnal cycles of adrenocorticotropic hormone and corticosterone secretion. We show that the staggerer mouse displays an enhanced endocrine response to novelty stress, which is not due to the enhanced production of interleukin-1 (IL-1), insofar as it is not blocked by pretreatment with IL-1ra and lacks the diurnal shift in corticosterone nonstressed levels; this last feature might be related to the expression of RORalpha in the SCN, a structure that maintains the circadian clock and plays a role in timing rhythmic physiology and behavior.