Correction of respiratory disorders in a mouse model of Rett syndrome

Ana Paula Abdala, Mathias Dutschmann, John M Bissonnette, Julian F R Paton

Research output: Contribution to journalArticle (Academic Journal)peer-review

137 Citations (Scopus)


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 neuron activity also reduces apnea, corrects the irregular breathing pattern, and prolongs survival in MeCP2 null males. Combining a GABA reuptake blocker with a serotonin 1a agonist in heterozygous females completely corrects their respiratory defects. The results indicate that GABA and serotonin 1a receptor activity are candidates for treatment of the respiratory disorders in Rett syndrome.
Translated title of the contributionCorrection of respiratory disorders in a mouse model of Rett syndrome
Original languageEnglish
Pages (from-to)18208 - 18213
Number of pages8
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number42
Publication statusPublished - 19 Oct 2010


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