Early abnormalities of post-sigh breathing in a mouse model of Rett syndrome.
Rett syndrome is a neurodevelopmental disease accompanied by complex, disabling symptoms, including breathing symptoms. Because Rett syndrome is caused by mutations in the transcriptional repressor methyl-CpG-binding protein 2 (MeCP2), Mecp2-deficient mice have been generated as experimental model. Males of Mecp2-deficient mice (Mecp2(-/y)) breathe normally at birth but show abnormal respiratory responses to hypoxia and hypercapnia from postnatal day 25 (P25). After P30, Mecp2(-/y) mice develop breathing symptoms reminiscent of Rett syndrome, aggravating until premature death at around P60. Using plethysmography, we analyzed the sighs and the post-sigh breathing pattern of unrestrained wild type male mice (WT) and Mecp2(-/y) mice from P15 to P60. Sighs are spontaneous large inspirations known to prevent lung atelectasis and to improve alveolar oxygenation. However, Mecp2(-/y) mice show early abnormalities of post-sigh breathing, with long-lasting post-sigh apnoeas, reduced tidal volume when eupnoea resumes and lack of post-sigh bradypnoea which develop from P15, aggravate with age and possibly contribute to breathing symptoms to come.
Voituron
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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
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S
Menuet
C
C
Lajard
A M
AM
Dutschmann
M
M
Hilaire
G
G
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001049:Apnea / Q000235:genetics / Q000503:physiopathology; D004195:Disease Models, Animal; D006934:Hypercalcemia / Q000150:complications* / Q000235:genetics; D000860:Hypoxia / Q000150:complications* / Q000235:genetics; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000172:deficiency*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010991:Plethysmography; D012119:Respiration / Q000235:genetics; D015656:Respiratory Mechanics / Q000235:genetics; D015619:Respiratory System Abnormalities / Q000235:genetics / Q000503:physiopathology*; D015518:Rett Syndrome / Q000235:genetics / Q000503:physiopathology*; D013990:Tidal Volume / Q000235:genetics
D051783:Methyl-CpG-Binding Protein 2