Ubiquitous Reactivation and Targeted Preservation of MeCP2 Expression in a Mouse Model of Rett Syndrome

Rett syndrome is a neurodevelopmental disorder that is predominately caused by mutations of the MECP2 gene. As neuronal apoptosis is not observed in RTT patients and MeCP2-deficient mice, the neurological deficits may be reversible. To address this, we reactivated MeCP2 expression ubiquitously in Me...

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Bibliographic Details
Main Author: Lang, Min
Other Authors: Eubanks, James
Language:en_ca
Published: 2012
Subjects:
Online Access:http://hdl.handle.net/1807/33301
Description
Summary:Rett syndrome is a neurodevelopmental disorder that is predominately caused by mutations of the MECP2 gene. As neuronal apoptosis is not observed in RTT patients and MeCP2-deficient mice, the neurological deficits may be reversible. To address this, we reactivated MeCP2 expression ubiquitously in MeCP2-deficient mice after symptom onset. Our results showed that life span, behavioural performances, EEG activity, thermoregulation, and daily rhythmic activity were significantly improved after MeCP2 reactivation. Furthermore, the extent of improvement was dependent upon the efficiency of MeCP2 reactivation. To assess the role of the catecholaminergic system in Rett syndrome pathophysiology, we selectively preserved MeCP2 function within tyrosine hydroxylase expressing cells. We observed a significant improvement in the life span of male rescue mice and reduced sudden unexplained death rates in female rescue mice. Behavioural performances and EEG patterns were also significantly improved.