{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T12:55:09Z","timestamp":1793451309506,"version":"4.5.0"},"reference-count":72,"publisher":"Society for Neuroscience","issue":"36","license":[{"start":{"date-parts":[[2012,3,7]],"date-time":"2012-03-07T00:00:00Z","timestamp":1331078400000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2011,9,7]]},"abstract":"<jats:p>\n                    Breathing is a spontaneous, rhythmic motor behavior critical for maintaining O\n                    <jats:sub>2<\/jats:sub>\n                    , CO\n                    <jats:sub>2<\/jats:sub>\n                    , and pH homeostasis. In mammals, it is generated by a neuronal network in the lower brainstem, the respiratory rhythm generator (Feldman et al., 2003). A century-old tenet in respiratory physiology posits that the respiratory chemoreflex, the stimulation of breathing by an increase in partial pressure of CO\n                    <jats:sub>2<\/jats:sub>\n                    in the blood, is indispensable for rhythmic breathing. Here we have revisited this postulate with the help of mouse genetics. We have engineered a conditional mouse mutant in which the toxic\n                    <jats:italic>\n                      PHOX2B\n                      <jats:sup>27Ala<\/jats:sup>\n                    <\/jats:italic>\n                    mutation that causes congenital central hypoventilation syndrome in man is targeted to the retrotrapezoid nucleus, a site essential for central chemosensitivity. The mutants lack a retrotrapezoid nucleus and their breathing is not stimulated by elevated CO\n                    <jats:sub>2<\/jats:sub>\n                    at least up to postnatal day 9 and they barely respond as juveniles, but nevertheless survive, breathe normally beyond the first days after birth, and maintain blood PCO\n                    <jats:sub>2<\/jats:sub>\n                    within the normal range. Input from peripheral chemoreceptors that sense PO\n                    <jats:sub>2<\/jats:sub>\n                    in the blood appears to compensate for the missing CO\n                    <jats:sub>2<\/jats:sub>\n                    response since silencing them by high O\n                    <jats:sub>2<\/jats:sub>\n                    abolishes rhythmic breathing. CO\n                    <jats:sub>2<\/jats:sub>\n                    chemosensitivity partially recovered in adulthood. Hence, during the early life of rodents, the excitatory input normally afforded by elevated CO\n                    <jats:sub>2<\/jats:sub>\n                    is dispensable for life-sustaining breathing and maintaining CO\n                    <jats:sub>2<\/jats:sub>\n                    homeostasis in the blood.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.1721-11.2011","type":"journal-article","created":{"date-parts":[[2011,9,7]],"date-time":"2011-09-07T14:54:38Z","timestamp":1315407278000},"page":"12880-12888","source":"Crossref","is-referenced-by-count":170,"title":["Breathing without CO\n                    <sub>2<\/sub>\n                    Chemosensitivity in Conditional\n                    <i>Phox2b<\/i>\n                    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