Loss of MeCP2 Function Across Several Neuronal Populations Impairs Breathing Response to Acute Hypoxia.

Frontiers in Neurology
Christopher S WardJeffrey L Neul

Abstract

Rett Syndrome (RTT) is a neurodevelopmental disorder caused by loss of function of the transcriptional regulator Methyl-CpG-Binding Protein 2 (MeCP2). In addition to the characteristic loss of hand function and spoken language after the first year of life, people with RTT also have a variety of physiological and autonomic abnormalities including disrupted breathing rhythms characterized by bouts of hyperventilation and an increased frequency of apnea. These breathing abnormalities, that likely involve alterations in both the circuitry underlying respiratory pace making and those underlying breathing response to environmental stimuli, may underlie the sudden unexpected death seen in a significant fraction of people with RTT. In fact, mice lacking MeCP2 function exhibit abnormal breathing rate response to acute hypoxia and maintain a persistently elevated breathing rate rather than showing typical hypoxic ventilatory decline that can be observed among their wild-type littermates. Using genetic and pharmacological tools to better understand the course of this abnormal hypoxic breathing rate response and the neurons driving it, we learned that the abnormal hypoxic breathing response is acquired as the animals mature, and that MeCP2...Continue Reading

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Citations

May 5, 2021·Genes, Brain, and Behavior·Bridget E CollinsJeffrey L Neul

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Key Resources (RRID) Mentioned

IMSR_JAX_007177
IMSR_JAX_006849
IMSR_JAX_003771
IMSR_JAX_016963
SCR_001622
SCR_017107
AB_2106783
SCR_002677
SCR_002865

Software Mentioned

SPSS
ImageJ
Ponemah3
Matlab
Axiovision

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