Reversal of neurological defects in a mouse model of Rett syndrome.
Rett syndrome is an autism spectrum disorder caused by mosaic expression of mutant copies of the X-linked MECP2 gene in neurons. However, neurons do not die, which suggests that this is not a neurodegenerative disorder. An important question for future therapeutic approaches to this and related disorders concerns phenotypic reversibility. Can viable but defective neurons be repaired, or is the damage done during development without normal MeCP2 irrevocable? Using a mouse model, we demonstrate robust phenotypic reversal, as activation of MeCP2 expression leads to striking loss of advanced neurological symptoms in both immature and mature adult animals.
Guy
Jacky
J
Wellcome Trust Centre for Cell Biology, Edinburgh University, King's Buildings, Edinburgh EH9 3JR, UK.
Gan
Jian
J
Selfridge
Jim
J
Cobb
Stuart
S
Bird
Adrian
A
D000818:Animals; D001921:Brain / Q000378:metabolism; D002678:Chimera; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D018390:Gene Targeting; D017774:Long-Term Potentiation; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000502:physiology*; D010641:Phenotype; D015518:Rett Syndrome / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy*; D009435:Synaptic Transmission; D013629:Tamoxifen / Q000494:pharmacology; D019076:Transgenes
C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D013629:Tamoxifen