| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ENVIRONMENTAL, EXERCISE, AND RESPIRATORY PHYSIOLOGY
1Institut National de la Santé et de la Recherche Médicale U676, Paris; 2Université Paris 7, Faculté de Médecine Denis Diderot, Institut Fédératif de Recherche 02, Paris; 3Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Service de Réanimation, Paris; 4Unité de Recherches sur les Adaptations Physiologiques et Comportementales, Université de Picardie, Amiens; and 5Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8542, Ecole Normale Supérieure, 46 rue d’Ulm, Paris, France
Submitted 14 December 2005 ; accepted in final form 3 January 2006
Heterozygous mutations of the transcription factor PHOX2B have been found in most patients with central congenital hypoventilation syndrome, a rare disease characterized by sleep-related hypoventilation and impaired chemosensitivity to sustained hypercapnia and sustained hypoxia. PHOX2B is a master regulator of autonomic reflex pathways, including peripheral chemosensitive pathways. In the present study, we used hyperoxic tests to assess the strength of the peripheral chemoreceptor tonic drive in Phox2b+/– newborn mice. We exposed 69 wild-type and 67 mutant mice to two hyperoxic tests (12-min air followed by 3-min 100% O2) 2 days after birth. Breathing variables were measured noninvasively using whole body flow plethysmography. The initial minute ventilation decrease was larger in mutant pups than in wild-type pups: –37% (SD 13) and –25% (SD 18), respectively, P < 0.0001. Furthermore, minute ventilation remained depressed throughout O2 exposure in mutants, possibly because of their previously reported impaired CO2 chemosensitivity, whereas it returned rapidly to the normoxic level in wild-type pups. Hyperoxia considerably increased total apnea duration in mutant compared with wild-type pups (P = 0.0001). A complementary experiment established that body temperature was not influenced by hyperoxia in either genotype group and, therefore, did not account for genotype-related differences in the hyperoxic ventilatory response. Thus partial loss of Phox2b function by heterozygosity did not diminish the tonic drive from peripheral chemoreceptors.
control of breathing; chemosensitivity; apnea
This article has been cited by other articles:
|
|
 |
|
  B. Bollen, M. Bouslama, B. Matrot, Y. Rotrou, G. Vardon, F. Lofaso, O. Van den Bergh, R. D'Hooge, and J. Gallego Cold stimulates the behavioral response to hypoxia in newborn mice Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2009; 296(5): R1503 - R1511. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Gaultier and J Gallego Neural control of breathing: insights from genetic mouse models J Appl Physiol, May 1, 2008; 104(5): 1522 - 1530. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Dubreuil, N. Ramanantsoa, D. Trochet, V. Vaubourg, J. Amiel, J. Gallego, J.-F. Brunet, and C. Goridis A human mutation in Phox2b causes lack of CO2 chemosensitivity, fatal central apnea, and specific loss of parafacial neurons PNAS, January 22, 2008; 105(3): 1067 - 1072. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Ramanantsoa, V. Vaubourg, B. Matrot, G. Vardon, S. Dauger, and J. Gallego Effects of temperature on ventilatory response to hypercapnia in newborn mice heterozygous for transcription factor Phox2b Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2007; 293(5): R2027 - R2035. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
