Adult neural function requires MeCP2 - PubMed (original) (raw)

Adult neural function requires MeCP2

Christopher M McGraw et al. Science. 2011.

Abstract

Rett syndrome (RTT) is a postnatal neurological disorder caused by mutations in MECP2, encoding the epigenetic regulator methyl-CpG-binding protein 2 (MeCP2). The onset of RTT symptoms during early life together with findings suggesting neurodevelopmental abnormalities in RTT and mouse models of RTT raised the question of whether maintaining MeCP2 function exclusively during early life might protect against disease. We show by using an inducible model of RTT that deletion of Mecp2 in adult mice recapitulates the germline knock-out phenotype, underscoring the ongoing role of MeCP2 in adult neurological function. Moreover, unlike the effects of other epigenetic instructions programmed during early life, the effects of early MeCP2 function are lost soon after its deletion. These findings suggest that therapies for RTT must be maintained throughout life.

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Figures

Figure 1. Adult deletion of Mecp2 recapitulates germline knock-out

(A–B) MeCP2 is depleted in adult knock-out (AKO) mice by western blot of brain lysates (A, N= 3–4 mice per genotype), and by immunofluorescence in cerebellum (B). Scale bar = 50um. (C) AKO mice display symptoms of disease. N= 6–12 per genotype. (D) AKO mice develop motor and learning impairments similar to germline Mecp2null/y (KO) mice. N=10–26 per genotype. (E) Sst and Grin2a mRNA levels are altered in AKO mice. N = 4–12 per genotype. (F) AKO mice die prematurely (left) similar to KO mice (right). N=10–26 per genotype. Data presented as mean ± s.e.m. (*) p<0.05, (**) p<0.01, or (***) p<0.001.

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Adult neural function requires MeCP2 - PubMed (original) (raw)