Reversal of Neurological Defects in a Mouse Model of Rett Syndrome

@article{Guy2007ReversalON,
  title={Reversal of Neurological Defects in a Mouse Model of Rett Syndrome},
  author={Jacky Guy and Jian Gan and Jim Selfridge and Stuart Cobb and Adrian Bird},
  journal={Science},
  year={2007},
  volume={315},
  pages={1143 - 1147}
}
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… Expand

Paper Mentions

Observational Clinical Trial
The purpose of this study is to advance understanding of the natural history of Rett syndrome (RTT), MECP2-duplication disorder (MECP2 Dup), CDKL5, FOXG1, and individuals with MECP2… Expand
ConditionsCDKL5 Disorder, FOXG1 Syndrome, MECP2 Duplication dIsorder, (+1 more)
Observational Clinical Trial
The overarching purpose of this study is to advance understanding of the natural history of Rett syndrome (RTT), MECP2-duplication disorder (MECP2 Dup), RTT-related disorders including… Expand
ConditionsCDKL5, FOXG1 Disorders, MECP2 Duplication, (+1 more)
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
Different strategies and the challenges of gene-based approaches in RTT are reviewed, including gene therapy, activation of MECP2 on the inactive X chromosome and read-through and repair of RTT-causing mutations. Expand
Early synaptic imbalance in genetic mice models of Autistic Spectrum Disorders
TLDR
Postnatal changes in synaptic transmission of neuroligin-1 deficient mice are investigated to find common patterns in postnatal maturation of synaptic transmission in these mice models in order to get an insight in the development of ASDs from early stages. Expand
The neural circuit basis of Rett syndrome
TLDR
It is proposed that Rett syndrome is a disorder of neural circuits as a result of non-linear accumulated dysfunction of synapses at the level of individual cell populations across multiple neurotransmitter systems and brain regions. Expand
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The overlapping delay before symptom onset in humans and mice raises the possibility that stability of brain function, not brain development per se, is compromised by the absence of MeCP2, and generates mice lacking Mecp2 using Cre-loxP technology. Expand
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Genotype/phenotype analysis revealed that the phenotypic spectrum of MECP2 mutations in humans is broader than initially suspected, and Rett syndrome is a prototype for the genetic, molecular, and neurobiological analysis of neurodevelopmental disorders. Expand
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The data demonstrate that MeCP2 levels must be tightly regulated in vivo, and that even mild overexpression of this protein is detrimental, and support the possibility that duplications or gain-of-function mutations in MECP2 might underlie some cases of X-linked delayed-onset neurobehavioral disorders. Expand
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TLDR
The hypothesis that the symptoms of RTT are exclusively caused by a neuronal MeCP2 deficiency is tested by placing Mecp2 expression under the control of a neuron-specific promoter and rescuing the RTT phenotype is tested. Expand
Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2
TLDR
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MECP2 is progressively expressed in post-migratory neurons and is involved in neuronal maturation rather than cell fate decisions
TLDR
Results indicate that MECP2 is involved in the maturation and maintenance of neurons, including dendritic arborization, rather than in cell fate decisions. Expand
Learning and Memory and Synaptic Plasticity Are Impaired in a Mouse Model of Rett Syndrome
TLDR
Very early symptomatic Mecp2308/Y mice had increased basal synaptic transmission and deficits in the induction of long-term depression, suggesting that functional and ultrastructural synaptic dysfunction is an early event in the pathogenesis of RTT. Expand
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TLDR
Together, these data provide the first evidence that the loss of Mecp2 expression is accompanied by age-dependent alterations in excitatory synaptic plasticity that are likely to contribute to the cognitive and functional deficits underlying Rett syndrome. Expand
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TLDR
The results indicate that the role of MECp2 is not restricted to the immature brain, but becomes critical in mature neurons, and that Mecp2 deficiency in these neurons is sufficient to cause neuronal dysfunction with symptomatic manifestation similar to Rett syndrome. Expand
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TLDR
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