Severely arrhythmic breathing is a hallmark of Rett syndrome (RTT) and 
profoundly affects quality of life for patients and their families. The last 
decade has seen the identification of the disease-causing gene, 
methyl-CpG-binding protein 2 (Mecp2) and the development of mouse models that 
phenocopy many aspects of the human syndrome, including breathing dysfunction. 
Recent studies have begun to characterize the breathing phenotype of Mecp2 
mutant mice and to define underlying electrophysiological and neurochemical 
deficits. The picture that is emerging is one of defects in synaptic 
transmission throughout the brainstem respiratory network associated with 
abnormal expression in several neurochemical signaling systems, including 
brain-derived neurotrophic factor (BDNF), biogenic amines and 
gamma-amino-butyric acid (GABA). Based on such findings, potential therapeutic 
strategies aimed at improving breathing by targeting deficits in neurochemical 
signaling are being explored. This review details our current understanding of 
respiratory dysfunction and underlying mechanisms in RTT with a particular focus 
on insights gained from mouse models.