Relevance to Autism

Mutations in the MECP2 gene underlie Rett syndrome, an autism spectrum disorder. Some studies have found that rare variations in the MECP2 gene are associated with autism, while others have looked and found no variants in autistic patients. It appears that EGR2 and MECP2 can regulate each other's expression (Swanberg et al., 2009).

Molecular Function

The encoded protein has methylation-dependent transcriptional repressor activity . It is also involved in regulation of RNA splicing.

External Links

References

Model Summary

Knockdown of mecp2 in zebrafish results in decreased axonal and dendritic architecture, which is likely driven by decreased expression of axonal guidance genes sema3f, sema5b, and robo2. Mecp2 morphants show increased apoptosis. They also exhibit reduced response to tactile stimuli even though the muscle fiber morphology is not changed. Mecp2 null mutants likewise show a decrease in dendritic architecture and decreased expression of sema3f, sema5b, and robo2. These effects in morpholino-induced morphants could be rescued by injection of mecp2 mRNA and ameliorated by injection of sema3f, sema5b, or robo2 mRNA. Loss of mecp2 also results in initial growth retardation and deficits in gastrointestinal function. These are accompanied by decreased in innate immune response measured in the number of neutrophils, but no change in the number of microglia or macrophages is observed. Likewise, mecp2 loss results in profound loss of tnfa function, a proinflammatory cytokine. Transient changes in il1b and il10 are observed as well, suggestive of increased inflammatory signaling, which are followed by resolution of inflammation. Injection of mecp2 mRNA temporarily increases mecp2 expression, but this effect is only temporary. Injection of tnfa mRNA does not rescue the immune response or the initial reduced growth deficits in mecp2-null mutants. Moreover, mecp2-null mutants show abnormal gene expression profile, measured by RNA sequencing.

References