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Effects of temperature on ventilatory response to hypercapnia in newborn mice heterozygous for transcription factor Phox2b.
Am J Physiol Regul Integr Comp Physiol. 2007 Nov; 293(5):R2027-35.AJ

Abstract

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 CO(2) sensitivity in a mouse model of CCHS. A weak response to CO(2) at thermoneutrality (32 degrees 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% CO(2) at three ambient temperatures (TAs): 29 degrees C, 32 degrees C, and 35 degrees 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 degrees 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.

Authors+Show Affiliations

Institut National de la Santé et de la Recherche Médicale, U676, Hôpital Robert Debré, Paris, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17715184

Citation

Ramanantsoa, N, et al. "Effects of Temperature On Ventilatory Response to Hypercapnia in Newborn Mice Heterozygous for Transcription Factor Phox2b." American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, vol. 293, no. 5, 2007, pp. R2027-35.
Ramanantsoa N, Vaubourg V, Matrot B, et al. Effects of temperature on ventilatory response to hypercapnia in newborn mice heterozygous for transcription factor Phox2b. Am J Physiol Regul Integr Comp Physiol. 2007;293(5):R2027-35.
Ramanantsoa, N., Vaubourg, V., Matrot, B., Vardon, G., Dauger, S., & Gallego, J. (2007). Effects of temperature on ventilatory response to hypercapnia in newborn mice heterozygous for transcription factor Phox2b. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 293(5), R2027-35.
Ramanantsoa N, et al. Effects of Temperature On Ventilatory Response to Hypercapnia in Newborn Mice Heterozygous for Transcription Factor Phox2b. Am J Physiol Regul Integr Comp Physiol. 2007;293(5):R2027-35. PubMed PMID: 17715184.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of temperature on ventilatory response to hypercapnia in newborn mice heterozygous for transcription factor Phox2b. AU - Ramanantsoa,N, AU - Vaubourg,V, AU - Matrot,B, AU - Vardon,G, AU - Dauger,S, AU - Gallego,J, Y1 - 2007/08/22/ PY - 2007/8/24/pubmed PY - 2007/12/27/medline PY - 2007/8/24/entrez SP - R2027 EP - 35 JF - American journal of physiology. Regulatory, integrative and comparative physiology JO - Am. J. Physiol. Regul. Integr. Comp. Physiol. VL - 293 IS - 5 N2 - 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 CO(2) sensitivity in a mouse model of CCHS. A weak response to CO(2) at thermoneutrality (32 degrees 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% CO(2) at three ambient temperatures (TAs): 29 degrees C, 32 degrees C, and 35 degrees 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 degrees 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. SN - 0363-6119 UR - https://www.unboundmedicine.com/medline/citation/17715184/Effects_of_temperature_on_ventilatory_response_to_hypercapnia_in_newborn_mice_heterozygous_for_transcription_factor_Phox2b_ L2 - http://www.physiology.org/doi/full/10.1152/ajpregu.00349.2007?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -