HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: 293/5/R2027    most recent 00349.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Ramanantsoa, N. Articles by Gallego, J. Search for Related Content PubMed PubMed Citation Articles by Ramanantsoa, N. Articles by Gallego, J.

ENVIRONMENTAL, EXERCISE AND RESPIRATORY PHYSIOLOGY

Effects of temperature on ventilatory response to hypercapnia in newborn mice heterozygous for transcription factor Phox2b

¹Institut National de la Santé et de la Recherche Médicale, U676, Hôpital Robert Debré, Paris, France; ²University Paris 7, Faculté de Médecine Denis Diderot, Paris, France; and ³Université de Picardie, Amiens, France; and ⁴Service de Pédiatrie-Réanimation, Hôpital Robert-Debré, Paris, France

Submitted 17 May 2007 ; accepted in final form 16 August 2007

Congenital central hypoventilation syndrome (CCHS) is a rare disease with variable severity, generally present from birth and chiefly characterized by impaired chemosensitivity to hypercapnia. The main cause of CCHS is a mutation in the PHOX2B gene, which encodes a transcription factor involved in the development of autonomic medullary reflex pathways. Temperature regulation is abnormal in many patients with CCHS. Here, we examined whether ambient temperature influenced CO₂ sensitivity in a mouse model of CCHS. A weak response to CO₂ at thermoneutrality (32°C) was noted previously in 2-day-old mice with an invalidated Phox2b allele (Phox2b+/–), compared with wild-type littermates. We exposed Phox2b+/– pups to 8% CO₂ at three ambient temperatures (TAs): 29°C, 32°C, and 35°C. We measured breathing variables and heart rate (HR) noninvasively using a novel whole body flow plethysmograph equipped with contact electrodes. Body temperature and baseline breathing increased similarly with TA in mutant and wild-type pups. The hypercapnic ventilatory response increased linearly with TA in both groups, while remaining smaller in mutant than in wild-type pups at all TAs. The differences between the absolute increases in ventilation in mutant and wild-type pups become more pronounced as temperature increased above 29°C. The ventilatory abnormalities in mutant pups were not associated with significant impairments of heart rate control. In both mutant and wild-type pups, baseline HR increased with TA. In conclusion, TA strongly influenced the hypercapnic ventilatory response in Phox2b+/– mutant mice. These findings suggest that abnormal temperature regulation may contribute to the severity of respiratory impairments in CCHS patients.

chemosensitivity; Ondine syndrome; congenital central hypoventilation syndrome; thermoregulation

This article has been cited by other articles:

				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]