Early breathing defects after moderate hypoxia or hypercapnia in a mouse model of Rett syndrome.
Rett syndrome (RTT) is a rare neurodevelopmental disease caused by mutations in the transcriptional repressor methyl-CpG-binding protein 2 (MeCP2) and accompanied by complex symptoms, including erratic breathing and life-threatening apnoeas. In Mecp2-deficient male mice (Mecp2(-/y)), breathing is normal at birth but becomes altered after postnatal day 30 (P30), with erratic rhythm and apnoeas aggravating until death at around P60. Using plethysmography, we analyzed breathing of unrestrained wild type mice and Mecp2(-/y) at P15, P25 and P30 under air and under short-lasting exposure to moderate hypoxia or hypercapnia. In Mecp2(-/y) with normal resting ventilation, we report exacerbated respiratory responses to hypoxia at P30 and transient apnoeas with erratic rhythm after hypoxia and hypercapnia at P30, P25 and occasionally P15. Then environmental factors may induce breathing defects well before than expected in Mecp2(-/y) and possibly in RTT patients. We therefore suggest avoiding exposure of young RTT patients to environmental situations where they may encounter moderate hypoxia or hypercapnia.
Voituron
Nicolas
N
Maturation, Plasticity, Physiology and Pathology of Respiration (mp3-resp team), Unité Mixte de Recherche 6231 CNRS, Faculté Saint-Jérôme, Service 362, 13397 Marseilles Cedex 20, France.
Zanella
Sébastien
S
Menuet
Clément
C
Dutschmann
Mathias
M
Hilaire
Gérard
G
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D006934:Hypercalcemia / Q000150:complications*; D000860:Hypoxia / Q000150:complications*; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000172:deficiency; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010991:Plethysmography / Q000379:methods; D012120:Respiration Disorders / Q000209:etiology* / Q000235:genetics; D015518:Rett Syndrome / Q000235:genetics / Q000503:physiopathology*
C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2