Abnormal inspiratory depth in Phox2a haploinsufficient mice
Neuroscience. 2007-03-01; 145(1): 384-392
DOI: 10.1016/j.neuroscience.2006.11.055
Lire sur PubMed
1. Neuroscience. 2007 Mar 2;145(1):384-92. Epub 2007 Jan 9.
Abnormal inspiratory depth in Phox2a haploinsufficient mice.
Wrobel LJ(1), Ogier M, Chatonnet F, Autran S, Mézières V, Thoby-Brisson M, McLean
H, Taeron C, Champagnat J.
Author information:
(1)Neurobiologie Génétique et Intégrative, UPR2216 CNRS, 1 Avenue de la Terrasse,
91198 Gif sur Yvette, France.
Mutations of genes encoding Phox2a or Phox2b transcription factors induce
modifications of different brainstem neuronal networks. Such modifications are
associated with defects in breathing behavior at birth. In particular, an
abnormal breathing frequency is observed in Phox2a-/- mutant mice, resulting from
abnormal development of the locus coeruleus (LC) nucleus. However, the role of
Phox2a proteins in the establishment of respiratory neuronal pathways is unknown,
largely because mutants die shortly after birth. In the present study, we
examined the effects of a haploinsufficiency of the Phox2a gene. Phox2a
heterozygotes survive and exhibit a significantly larger inspiratory volume both
during normoxic breathing and in response to hypoxia and a delayed maturation of
inspiratory duration compared to wild-type animals. This phenotype accompanied by
an unaltered frequency is evident at birth and persists until at least postnatal
day 10. Morphological analyses of Phox2a+/- animals revealed no anomaly in the LC
region, but highlighted an increase in the number of cells expressing tyrosine
hydroxylase enzyme, a marker of chemoafferent neurons, in the petrosal sensory
ganglion. These data indicate that Phox2a plays a critical role in the ontogeny
of the reflex control of inspiration.
DOI: 10.1016/j.neuroscience.2006.11.055
PMID: 17218061 [Indexed for MEDLINE]