title: Sleep-disordered breathing in newborn mice heterozygous for the transcription factor Phox2b.
abstract: BACKGROUND
  Central congenital hypoventilation syndrome (CCHS) is a rare autosomal dominant syndrome present from birth, and characterized by depressed ventilation during sleep. Heterozygous mutations of the homeobox gene Phox2b were recently found in a very high proportion of patients.
  
  
  OBJECTIVE
  To determine whether newborn mice with heterozygous targeted deletion of the transcription factor Phox2b would display sleep-disordered breathing.
  
  
  METHODS
  We measured breathing pattern using whole-body plethysmography in wild-type and mutant 5-day-old mice, and we classified sleep-wake states using nuchal EMG and behavioral scores.
  
  
  RESULTS
  We found that sleep apnea total time was approximately six times longer (8.9 +/- 12 vs. 1.5 +/- 2.2 seconds, p < 0.0015), and ventilation during active sleep was 21% lower (18.4 +/- 5.1 vs. 23.3 +/- 5.5 ml/g/second, p < 0.006) in mutant than in wild-type pups. During wakefulness, apnea time and ventilation were not significantly different between mutant and wild-type pups. Mutant and wild-type pups showed highly similar sleep-wake states.
  
  
  CONCLUSIONS
  Although their respiratory phenotype was much less severe than CCHS, the Phox2b(+/-) mutant mice showed sleep-disordered breathing, which partially modeled the key feature of CCHS.
authors.affiliation: INSERM U676, Hôpital Robert-Debré, 48 Boulevard Sérurier, 75019 Paris, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Durand
authors.forename: Stéphane
authors.initials: S
authors.lastname: Dauger
authors.forename: Alexandre
authors.initials: A
authors.lastname: Pattyn
authors.forename: Claude
authors.initials: C
authors.lastname: Gaultier
authors.forename: Christo
authors.initials: C
authors.lastname: Goridis
authors.forename: Jorge
authors.initials: J
authors.lastname: Gallego
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001835:Body Weight; D004576:Electromyography; D017353:Gene Deletion; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000235:genetics*; D051379:Mice; D012119:Respiration; D012890:Sleep; D012891:Sleep Apnea Syndromes / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D012894:Sleep Stages; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C109220:NBPhox protein; D014157:Transcription Factors