The disruption of circadian rhythmicity of gene expression in the hippocampus and associated structures in Gria2R/R mice; a comparison with C57BL/6J and Adar2-/- mice strains

Abstract

Adar2^-/- mice are a widely used model for studying the physiological consequences of reduced RNA editing. These mice are viable only when the Q/R editing site of the Gria2 subunit of the AMPA receptor is constitutively mutated to the codon for arginine, and Gria2^R/R mice often serve as the sole control for Adar2^-/- mice. Our study aimed to investigate whether ADAR2 inactivity and the Gria2^R/R phenotype affect the rhythmicity of the circadian clock gene pattern and the expression of Gria1 and Gria2 subunits in the suprachiasmatic nucleus (SCN), hippocampus, parietal cortex and liver. Our data show that Gria2^R/R mice completely lost circadian rhythmicity in the hippocampus compared to Adar2^-/- mice. Compared to C57BL/6J mice, the expression profiles in the hippocampus and parietal cortex of Gria2^R/R mice differ to the same extent as in Adar2^-/-. No alterations were detected in the circadian profiles in the livers. These data suggest that the natural gradual postnatal increase in the editing of the Q/R site of the Gria2 subunit may be important for the development of circadian clockwork in some brain structures, and the use of Gria2^R/R mice as the only control to Adar2^-/- mice in the experiments dependent on the hippocampus and parietal cortex should therefore be considered.

Keywords: Adar2; Circadian rhythms; Gria2; Hippocampus; Mice; Suprachiasmatic nucleus.