Unknown

Dataset Information

0

Postnatal inactivation reveals enhanced requirement for MeCP2 at distinct age windows.


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.

SUBMITTER: Cheval H 

PROVIDER: S-EPMC3412380 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

altmetric image

Publications

Postnatal inactivation reveals enhanced requirement for MeCP2 at distinct age windows.

Cheval Hélène H   Guy Jacky J   Merusi Cara C   De Sousa Dina D   Selfridge Jim J   Bird Adrian A  

Human molecular genetics 20120531 17


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 deat  ...[more]

Similar Datasets

| S-EPMC4309268 | biostudies-literature
| S-EPMC1794312 | biostudies-literature
| S-EPMC5560866 | biostudies-literature
| S-EPMC7657357 | biostudies-literature
| S-EPMC9033237 | biostudies-literature
| S-EPMC2614877 | biostudies-literature
| S-EPMC2897782 | biostudies-literature
| S-EPMC8794850 | biostudies-literature
| S-EPMC7080408 | biostudies-literature
| S-EPMC3100687 | biostudies-literature