Breathing without CO2 Chemosensitivity in Conditional Phox2b Mutants

N. Ramanantsoa, M.-R. Hirsch, M. Thoby-Brisson, V. Dubreuil, J. Bouvier, P.-L. Ruffault, B. Matrot, G. Fortin, J.-F. Brunet, J. Gallego, C. Goridis
Journal of Neuroscience. 2011-09-07; 31(36): 12880-12888
DOI: 10.1523/jneurosci.1721-11.2011

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1. J Neurosci. 2011 Sep 7;31(36):12880-8. doi: 10.1523/JNEUROSCI.1721-11.2011.

Breathing without CO(2) chemosensitivity in conditional Phox2b mutants.

Ramanantsoa N(1), Hirsch MR, Thoby-Brisson M, Dubreuil V, Bouvier J, Ruffault PL,
Matrot B, Fortin G, Brunet JF, Gallego J, Goridis C.

Author information:
(1)Institut National de la Santé et de la Recherche Médicale (INSERM) U676,
Hôpital Robert Debré, 75019 Paris, France.

Breathing is a spontaneous, rhythmic motor behavior critical for maintaining
O(2), CO(2), 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(2) 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 PHOX2B(27Ala) 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(2) 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(2) within the normal range. Input from peripheral
chemoreceptors that sense PO(2) in the blood appears to compensate for the
missing CO(2) response since silencing them by high O(2) abolishes rhythmic
breathing. CO(2) chemosensitivity partially recovered in adulthood. Hence, during
the early life of rodents, the excitatory input normally afforded by elevated
CO(2) is dispensable for life-sustaining breathing and maintaining CO(2)
homeostasis in the blood.

DOI: 10.1523/JNEUROSCI.1721-11.2011
PMCID: PMC6623392
PMID: 21900566 [Indexed for MEDLINE]

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