| First Author | Kline DD | Year | 2002 |
| Journal | Proc Natl Acad Sci U S A | Volume | 99 |
| Issue | 2 | Pages | 821-6 |
| PubMed ID | 11792862 | Mgi Jnum | J:73981 |
| Mgi Id | MGI:2157266 | Doi | 10.1073/pnas.022634199 |
| Citation | Kline DD, et al. (2002) Defective carotid body function and impaired ventilatory responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor 1alpha. Proc Natl Acad Sci U S A 99(2):821-6 |
| abstractText | To investigate whether the transcriptional activator hypoxia-inducible factor 1 (HIF-1) is required for ventilatory responses to hypoxia, we analyzed mice that were either wild type or heterozygous for a loss-of-function (knockout) allele at the Hif1a locus, which encodes the O(2)-regulated HIF-1alpha subunit. Although the ventilatory response to acute hypoxia was not impaired in Hif1a(+/-) mice, the response was primarily mediated via vagal afferents, whereas in wild-type mice, carotid body chemoreceptors played a predominant role. When carotid bodies isolated from wild-type mice were exposed to either cyanide or hypoxia, a marked increase in sinus nerve activity was recorded, whereas carotid bodies from Hif1a(+/-) mice responded to cyanide but not to hypoxia. Histologic analysis revealed no abnormalities of carotid body morphology in Hif1a(+/-) mice. Wild-type mice exposed to hypoxia for 3 days manifested an augmented ventilatory response to a subsequent acute hypoxic challenge. In contrast, prior chronic hypoxia resulted in a diminished ventilatory response to acute hypoxia in Hif1a(+/-) mice. Thus partial HIF-1alpha deficiency has a dramatic effect on carotid body neural activity and ventilatory adaptation to chronic hypoxia. |
