| First Author | Cheval H | Year | 2012 |
| Journal | Hum Mol Genet | Volume | 21 |
| Issue | 17 | Pages | 3806-14 |
| PubMed ID | 22653753 | Mgi Jnum | J:185982 |
| Mgi Id | MGI:5430699 | Doi | 10.1093/hmg/dds208 |
| Citation | Cheval H, et al. (2012) Postnatal inactivation reveals enhanced requirement for MeCP2 at distinct age windows. Hum Mol Genet 21(17):3806-14 |
| abstractText | 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 approximately 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. |
