Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Published Online February 8, 2007
Science DOI: 10.1126/science.1138389

Reports

Submitted on December 4, 2006
Accepted on January 18, 2007

Reversal of Neurological Defects in a Mouse Model of Rett Syndrome

Jacky Guy 1, Jian Gan 2, Jim Selfridge 1, Stuart Cobb 2, Adrian Bird 1*

1 Wellcome Trust Centre for Cell Biology, Edinburgh University, The King's Buildings, Edinburgh EH9 3JR, UK.
2 Neuroscience and Biomedical Systems, Institute of Biomedical and Life Sciences, West Medical Building, University of Glasgow, Glasgow G12 8QQ, UK.

* To whom correspondence should be addressed.
Adrian Bird , E-mail: a.bird{at}ed.ac.uk

Rett syndrome is an autism spectrum disorder caused by mosaic expression of mutant copies of the X-linked MECP2 gene in neurons. Neuronal death is absent, suggesting 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.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Synaptic Circuit Abnormalities of Motor-Frontal Layer 2/3 Pyramidal Neurons in an RNA Interference Model of Methyl-CpG-Binding Protein 2 Deficiency.
L. Wood, N. W. Gray, Z. Zhou, M. E. Greenberg, and G. M. G. Shepherd (2009)
J. Neurosci. 29, 12440-12448
   Abstract »    Full Text »    PDF »
Intact Long-Term Potentiation but Reduced Connectivity between Neocortical Layer 5 Pyramidal Neurons in a Mouse Model of Rett Syndrome.
V. S. Dani and S. B. Nelson (2009)
J. Neurosci. 29, 11263-11270
   Abstract »    Full Text »    PDF »
Rett Syndrome Astrocytes Are Abnormal and Spread MeCP2 Deficiency through Gap Junctions.
I. Maezawa, S. Swanberg, D. Harvey, J. M. LaSalle, and L.-W. Jin (2009)
J. Neurosci. 29, 5051-5061
   Abstract »    Full Text »    PDF »
MeCP2 involvement in the regulation of neuronal {alpha}-tubulin production.
L. Abuhatzira, R. Shemer, and A. Razin (2009)
Hum. Mol. Genet. 18, 1415-1423
   Abstract »    Full Text »    PDF »
MeCP2-Mediated Transcription Repression in the Basolateral Amygdala May Underlie Heightened Anxiety in a Mouse Model of Rett Syndrome.
M. Adachi, A. E. Autry, H. E. Covington III, and L. M. Monteggia (2009)
J. Neurosci. 29, 4218-4227
   Abstract »    Full Text »    PDF »
From the Cover: Phosphorylation of MeCP2 at Serine 80 regulates its chromatin association and neurological function.
J. Tao, K. Hu, Q. Chang, H. Wu, N. E. Sherman, K. Martinowich, R. J. Klose, C. Schanen, R. Jaenisch, W. Wang, et al. (2009)
PNAS 106, 4882-4887
   Abstract »    Full Text »    PDF »
Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice.
D. Tropea, E. Giacometti, N. R. Wilson, C. Beard, C. McCurry, D. D. Fu, R. Flannery, R. Jaenisch, and M. Sur (2009)
PNAS 106, 2029-2034
   Abstract »    Full Text »    PDF »
Transcriptional regulation and stabilization of left-right neuronal identity in C. elegans.
B. J. Lesch, A. R. Gehrke, M. L. Bulyk, and C. I. Bargmann (2009)
Genes & Dev. 23, 345-358
   Abstract »    Full Text »    PDF »
MECP2 genomic structure and function: insights from ENCODE.
J. Singh, A. Saxena, J. Christodoulou, and D. Ravine (2008)
Nucleic Acids Res. 36, 6035-6047
   Abstract »    Full Text »    PDF »
Rett Syndrome-causing Mutations in Human MeCP2 Result in Diverse Structural Changes That Impact Folding and DNA Interactions.
R. P. Ghosh, R. A. Horowitz-Scherer, T. Nikitina, L. M. Gierasch, and C. L. Woodcock (2008)
J. Biol. Chem. 283, 20523-20534
   Abstract »    Full Text »    PDF »
Defective body-weight regulation, motor control and abnormal social interactions in Mecp2 hypomorphic mice.
B. Kerr, M. Alvarez-Saavedra, M. A. Saez, A. Saona, and J. I. Young (2008)
Hum. Mol. Genet. 17, 1707-1717
   Abstract »    Full Text »    PDF »
Targeted delivery of an Mecp2 transgene to forebrain neurons improves the behavior of female Mecp2-deficient mice.
D. G.M. Jugloff, K. Vandamme, R. Logan, N. P. Visanji, J. M. Brotchie, and J. H. Eubanks (2008)
Hum. Mol. Genet. 17, 1386-1396
   Abstract »    Full Text »    PDF »
Rett Syndrome: Recent Research Progress.
A. K. Percy (2008)
J Child Neurol 23, 543-549
   Abstract »    PDF »
Reduced social interaction and ultrasonic communication in a mouse model of monogenic heritable autism.
S. Jamain, K. Radyushkin, K. Hammerschmidt, S. Granon, S. Boretius, F. Varoqueaux, N. Ramanantsoa, J. Gallego, A. Ronnenberg, D. Winter, et al. (2008)
PNAS 105, 1710-1715
   Abstract »    Full Text »    PDF »
Effect of inspired oxygen on periodic breathing in methy-CpG-binding protein 2 (Mecp2) deficient mice.
J. M. Bissonnette and S. J. Knopp (2008)
J Appl Physiol 104, 198-204
   Abstract »    Full Text »    PDF »
Integrated epigenomic analyses of neuronal MeCP2 reveal a role for long-range interaction with active genes.
D. H. Yasui, S. Peddada, M. C. Bieda, R. O. Vallero, A. Hogart, R. P. Nagarajan, K. N. Thatcher, P. J. Farnham, and J. M. LaSalle (2007)
PNAS 104, 19416-19421
   Abstract »    Full Text »    PDF »
Brain-Derived Neurotrophic Factor Expression and Respiratory Function Improve after Ampakine Treatment in a Mouse Model of Rett Syndrome.
M. Ogier, H. Wang, E. Hong, Q. Wang, M. E. Greenberg, and D. M. Katz (2007)
J. Neurosci. 27, 10912-10917
   Abstract »    Full Text »    PDF »
Cell-specific expression of wild-type MeCP2 in mouse models of Rett syndrome yields insight about pathogenesis.
M. Alvarez-Saavedra, M. A. Saez, D. Kang, H. Y. Zoghbi, and J. I. Young (2007)
Hum. Mol. Genet. 16, 2315-2325
   Abstract »    Full Text »    PDF »
Disease Mechanisms in Neuroscience.
(2007)
Neuroscientist 13, 302
   PDF »
The Possible Interplay of Synaptic and Clock Genes in Autism Spectrum Disorders.
T. Bourgeron (2007)
Cold Spring Harb Symp Quant Biol 72, 645-654
   Abstract »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)