Journal article

Correction of respiratory disorders in a mouse model of Rett syndrome

Ana PL Abdala, Mathias Dutschmann, John M Bissonnette, Julian FR Paton

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | NATL ACAD SCIENCES | Published : 2010

Abstract

Rett syndrome (RTT) is an autism spectrum disorder caused by mutations in the X-linked gene that encodes the transcription factor methyl-CpG-binding protein 2 (MeCP2). A major debilitating phenotype in affected females is frequent apneas, and heterozygous Mecp2-deficient female mice mimic the human respiratory disorder. GABA defects have been demonstrated in the brainstem of Mecp2-deficient mice. Here, using an intact respiratory network, we show that apnea in RTT mice is characterized by excessive excitatory activity in expiratory cranial and spinal nerves. Augmenting GABA markedly improves the respiratory phenotype. In addition, a serotonin 1a receptor agonist that depresses expiratory neu..

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Grants

Awarded by March of Dimes Foundation


Awarded by International Rett Syndrome Foundation


Awarded by National Institutes of Health


Awarded by NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE


Funding Acknowledgements

We thank Sharon Knopp for technical assistance and Victoria Jenkins and Caitlin Monaghan for genotyping mice. This work was supported by March of Dimes Foundation Grant 6-FY06-314 (to J.M.B.), International Rett Syndrome Foundation Grant 0802 (to J.M.B. and J.F.R.P.), and National Institutes of Health Grant NS057815 (to J.F.R.P.). J.F.R.P. was in receipt of a Royal Society Wolfson Research Merit Award. J.M.B. received a Benjamin Meaker visiting fellowship from the University of Bristol.