Postnatal inactivation reveals enhanced requirement for MeCP2 at distinct age windows

Hélène Cheval, Jacky Guy, Cara Merusi, Dina De Sousa, Jim Selfridge, Adrian Bird

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Pages (from-to)3806-3814
JournalHuman Molecular Genetics
Issue number17
Publication statusPublished - 2012


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