Human Molecular Genetics Advance Access published online on July 17, 2007
Human Molecular Genetics, doi:10.1093/hmg/ddm185
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Cell-specific expression of wild-type MeCP2 in mouse models of Rett syndrome yields insight about pathogenesis
1 Centro de Estudios Científicos, Valdivia, 5110246, Chile 2 Universidad Austral de Chile, Valdivia, 905-9100, Chile 3 Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA 4 Department of Molecular and Human Genetics, Baylor College of MedicineHouston, TX 77030, USA 5 Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA
* To whom correspondence should be addressed. Tel: +56 63 234569; Fax: +56 63 234517; Email: jyoung{at}cecs.cl
Received May 7, 2007; Revised July 8, 2007; Accepted July 8, 2007
Rett syndrome (RTT), a leading cause of mental retardation with autistic features in females, is caused by mutations in the gene encoding methyl-CPG-binding protein 2 (MeCP2). Rett syndrome is characterized by a diverse set of neurological features that includes cognitive, motor, behavioral, and autonomic disturbances. The diverse features suggest that specific neurons contribute to particular phenotypes and raise the question whether restoring MeCP2 function in a cell-specific manner will rescue some of the phenotypes seen in Rett syndrome. To address this, we generated transgenic mice expressing inducible MeCP2 under the control of the brain specific promoters calcium/calmodulin-dependent protein kinase II (CamKII) or neuron specific enolase (Eno2) and bred them onto mouse models lacking functional MeCP2. Expression of normal MeCP2 in either CamKII or Eno2 distribution, was unable to prevent the appearance of most of the phenotypes of the RTT mouse models. These results suggest that most RTT phenotypes are caused either by disruption of complex neural networks involving neurons throughout the brain, or by disruption of the function of specific neurons outside of the broad CamKII or Eno2 distribution.
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