unconventional transcriptional response to environmental enrichment in a mouse model of rett syndrome非传统的转录反应环境浓缩rett综合症的小鼠模型.pdf

Unconventional Transcriptional Response to Environmental Enrichment in a Mouse Model of Rett Syndrome 1 1,2 1,2,3,4 1,3,4 Bredford Kerr , Pamela A. Silva , Katherina Walz , Juan I. Young * ´ 1 Department of Biology, Centro de Estudios Cientıficos, Valdivia, Chile, 2 Department of Biochemistry, Universidad Austral de Chile, Valdivia, Chile, 3 CIN (Centro de ´ ´ Ingenierıa de la Innovacion del CECS), Valdivia, Chile, 4 Department of Human Genetics, John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, Florida, United States of America Abstract Background: Rett syndrome (RTT) is an X-linked postnatal neurodevelopmental disorder caused by mutations in the gene encoding methyl-CpG binding protein 2 (MeCP2) and one of the leading causes of mental retardation in females. RTT is characterized by psychomotor retardation, purposeless hand movements, autistic-like behavior and abnormal gait. We studied the effects of environmental enrichment (EE) on the phenotypic manifestations of a RTT mouse model that lacks MeCP2 (Mecp22/y). Principal Findings: We found that EE delayed and attenuated some neurological alterations presented by Mecp22/y mice and prevented the development of motor discoordination and anxiety-related abnormalities. To define the molecular correlate of this beneficial effect of EE, we analyzed the expression of several synaptic marker genes whose expression is increased by EE in several mouse models. Conclusions/Significance: We found that EE induced downregulation of several synaptic