Author(s): Cheval H, Guy J, Merusi C, De Sousa D, Selfridge J,
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Abstract Rett Syndrome is a neurological disorder caused by mutations in the X-linked MECP2 gene. Mouse models where Mecp2 is inactivated or mutated recapitulate several features of the disorder and have demonstrated a requirement for the protein to ensure brain function in adult mice. We deleted the Mecp2 gene in ~80\% of brain cells at three postnatal ages to determine whether the need for MeCP2 varies with age. Inactivation at all three time points induced Rett-like phenotypes and caused premature death of the animals. We find two threshold ages beyond which the requirement for MeCP2 markedly increases in stringency. The earlier threshold (8-14 weeks), when inactivated mice develop symptoms, represents early adulthood in the mouse and coincides with the period when Mecp2-null mice exhibit terminal symptoms. Unexpectedly, we identified a later age threshold (30-45 weeks) beyond which an 80\% reduction in MeCP2 is incompatible with life. This finding suggests an enhanced role for MeCP2 in the aging brain.
This article was published in Hum Mol Genet
and referenced in Autism-Open Access