Regional MeCP2 expression levels in the female MeCP2-deficient mouse brain correlate with specific behavioral impairments

Abstract

Using female MeCP2-deficient mice as a model, we tested whether MeCP2 expression levels would parallel one another in different regions of the brain and spinal cord, and/or whether the levels of MeCP2 protein in these specific neural regions would correlate with the degree of behavioral impairment seen in individual subjects. Our results show that MeCP2 protein levels are not uniform across different regions of the mosaic brain, and that the relative MeCP2 levels in one region did not necessarily predict its expression levels in other regions of the same mouse. Correlational analysis between region-specific MeCP2 expression levels and the degree of impairment exhibited by mice in specific behavioral tests revealed significant associations. Cortical MeCP2 expression was significantly correlated with general symptomatic severity and daily EEG delta power patterning. Hippocampal MeCP2 expression was significantly correlated with exploratory activity behaviors, anxiety-like behaviors, and epileptiform discharge rates, whereas cerebellar and spinal cord MeCP2 expression levels correlated only with daily EEG delta power patterning. Collectively, our results show that MeCP2 protein expression in female MeCP2-deficient mice is not uniform throughout specific brain regions, and indicate that specific behavioral deficits in these mice may correlate with the region-specific expression levels of the functional MeCP2 allele.