Unconventional transcriptional response to environmental enrichment in a mouse model of Rett syndrome.
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 (Mecp2(-/y)).


RESULTS
We found that EE delayed and attenuated some neurological alterations presented by Mecp2(-/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
We found that EE induced downregulation of several synaptic markers, suggesting that the partial prevention of RTT-associated phenotypes is achieved through a non-conventional transcriptional program.
Kerr
Bredford
B
Department of Biology, Centro de Estudios Científicos, Valdivia, Chile.
Silva
Pamela A
PA
Walz
Katherina
K
Young
Juan I
JI
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D004195:Disease Models, Animal; D004777:Environment; D018782:Maze Learning / Q000502:physiology; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D010641:Phenotype; D011897:Random Allocation; D015518:Rett Syndrome / Q000235:genetics* / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2