Systematically review the abnormalities in event related potential (ERP) recorded in Rett Syndrome (RTT) patients and animals in search of translational biomarkers of deficits related to the particular neurophysiological processes of known genetic origin (MECP2 mutations).
Our study sheds light on the relevance of the protein-regulation of main physiological process in the complex mechanisms leading from Mecp2 mutation to the RTT clinical phenotype.
In Mecp2-null rats, abnormalities in breathing patterns were apparent in both decerebrate rats and awake animals, suggesting that RTT-type breathing abnormalities take place in the brainstem without forebrain input.
Cross-sectional and longitudinal data were collected from 861 females with RTT and from 48 females who have MECP2 mutations without meeting criteria for RTT.
Rett syndrome (RTT) is one of the most common causes of intellectual and developmental disabilities in girls, and is caused by mutations in the gene encoding methyl-CpG binding protein 2 (MECP2).
Here, we review the experimental evidence demonstrating that alterations in the levels and functionality of the methylated DNA-binding transcriptional regulator MeCP2 are implicated in the learning and memory deficits present in mouse models of Rett syndrome and <i>MECP2</i> duplication syndrome.
Rett syndrome (RTT) is an early-onset neurodevelopmental disorder that is caused by mutations in the MECP2 gene; however, defects in other genes (CDKL5 and FOXG1) can lead to presentations that resemble classic RTT, although they are not completely identical.
Although the alterations seen in mouse models of RTT appear to be primarily due to cell-autonomous effects, there are also non-cell autonomous mechanisms including those caused by MeCP2-deficient glia that negatively impact healthy neuronal function.
In this study, female heterozygous Mecp2-null mice (Mecp2+/- mice), a model of RTT, were fed a normal chow diet or high-fat diet (HFD), and the changes in molecular signaling pathways were investigated.
We show that this approach can be used to introduce PTMs and biochemical probes into a range of proteins including Cas9 nuclease and the transcriptional regulator MeCP2, which causes Rett syndrome when mutated.
Mouse models of MeCP2 dysfunction that have been developed are thus important not only for examining the protein's contribution to RTT, but also for elucidating the etiologies of other MECP2-associated neuropsychiatric disorders.