Carotid Body Dysfunction Contributes to Respiratory Dysfunction in Rett Syndrome

Disordered breathing is a hallmark feature of RTT that negatively impacts quality of life and can be life-threatening. Despite this, mechanisms underlying disordered breathing in RTT are poorly understood.

Although RTT is primarily considered a central nervous system disorder, we found that increased drive from peripheral respiratory chemoreceptors may contribute to unstable breathing in MeCP2 deficient mice. Consistent with this, breathing pure oxygen to limit output of peripheral chemoreceptors stabilized breathing in MeCP2 deficient mice. Also, knockdown of MeCP2 within the carotid body recapitulates RTT-like unstable breathing.