Abstract |
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.
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Authors | N Ramanantsoa, V Vaubourg, S Dauger, B Matrot, G Vardon, Z Chettouh, C Gaultier, C Goridis, J Gallego |
Journal | American journal of physiology. Regulatory, integrative and comparative physiology
(Am J Physiol Regul Integr Comp Physiol)
Vol. 290
Issue 6
Pg. R1691-6
(Jun 2006)
ISSN: 0363-6119 [Print] United States |
PMID | 16410396
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Homeodomain Proteins
- NBPhox protein
- Transcription Factors
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Topics |
- Animals
- Animals, Newborn
- Apnea
(genetics, physiopathology)
- Body Temperature
(genetics, physiology)
- Female
- Heterozygote
- Homeodomain Proteins
(genetics)
- Hyperoxia
(physiopathology)
- Male
- Mice
- Mice, Mutant Strains
- Plethysmography, Whole Body
- Pulmonary Ventilation
(genetics, physiology)
- Tidal Volume
(genetics, physiology)
- Transcription Factors
(genetics)
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