The disturbance of circadian rhythmicity of clock gene expression in Gria2R/R mice; the comparison with C57BL/6J and Adar2-/- mice strains

Adar2 -/- mice are a widely used model to study 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. The aim of our study was to investigate whether ADAR2 inactivity and the Gria2 R/R phenotype affect the rhythmicity of the pattern of circadian clock genes 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, expression profiles in hippocampus and parietal cortex of Gria2 R/R mice differ to the same extent as in Adar2 -/- . These data suggest that the natural gradual increase in the editing of the Q/R site of the Gria2 subunit postnatally 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 hippocampus- and parietal cortex- dependent experiments should therefore be considered.