| First Author | Ramanantsoa N | Year | 2006 |
| Journal | Am J Physiol Regul Integr Comp Physiol | Volume | 290 |
| Issue | 6 | Pages | R1691-6 |
| PubMed ID | 16410396 | Mgi Jnum | J:108630 |
| Mgi Id | MGI:3624452 | Doi | 10.1152/ajpregu.00875.2005 |
| Citation | Ramanantsoa N, et al. (2006) Ventilatory response to hyperoxia in newborn mice heterozygous for the transcription factor Phox2b. Am J Physiol Regul Integr Comp Physiol 290(6):R1691-6 |
| abstractText | 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% O(2)) 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 O(2) exposure in mutants, possibly because of their previously reported impaired CO(2) 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. |
