Defects in brainstem neurons associated with breathing and motor function in the Mecp2R168X/Y mouse model of Rett syndrome

Rett Syndrome (RTT) is an X-linked neurodevelopmental disorder caused mostly by disruption of the MECP2 gene. Among several RTT-like mouse models, one of them is a strain of mice that carries an R168X point mutation in Mecp2 and resembles one of the most common RTT-causing mutations in humans. Although several behavioral defects have previously been found in the Mecp2R168X/Y mice, alterations in nerve cells remain unknown. Here we compare several behavioral and cellular outcomes between this Mecp2R168X/Y model and a widely used Mecp2Bird/Y mouse model. With lower body weight and shorter lifespan than their wild-type littermates, the Mecp2R168X/Y mice showed impairments of breathing and motor function. Thus we studied brainstem CO2-chemosensitive neurons and propriosensory cells that are associated with these two functions, respectively. Neurons in the locus coeruleus (LC) of both mutant strains showed defects in their intrinsic membrane properties, including changes in action potential morphology and exce...