{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:19:23Z","timestamp":1791245963998,"version":"4.1.0"},"reference-count":34,"publisher":"National Academy of Sciences","issue":"2","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,1,22]]},"abstract":"<jats:p>\n                    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\n                    <jats:italic>Hif1a<\/jats:italic>\n                    locus, which encodes the O\n                    <jats:sub>2<\/jats:sub>\n                    -regulated HIF-1\u03b1 subunit. Although the ventilatory response to acute hypoxia was not impaired in\n                    <jats:italic>Hif1a<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    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\n                    <jats:italic>Hif1a<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice responded to cyanide but not to hypoxia. Histologic analysis revealed no abnormalities of carotid body morphology in\n                    <jats:italic>Hif1a<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    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\n                    <jats:italic>Hif1a<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice. Thus partial HIF-1\u03b1 deficiency has a dramatic effect on carotid body neural activity and ventilatory adaptation to chronic hypoxia.\n                  <\/jats:p>","DOI":"10.1073\/pnas.022634199","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:36:44Z","timestamp":1027679804000},"page":"821-826","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":242,"title":["Defective carotid body function and impaired ventilatory responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor 1\u03b1"],"prefix":"10.1073","volume":"99","author":[{"given":"David D.","family":"Kline","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH 44106; and McKusick\u2013Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Jie","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH 44106; and McKusick\u2013Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominador J.","family":"Manalo","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH 44106; and McKusick\u2013Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregg L.","family":"Semenza","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, 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