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Congenital hypoventilation and impaired hypoxic response in Nurr1 mutant mice
Author(s) -
Nsegbe Elise,
WallénMackenzie Åsa,
Dauger Stephane,
Roux JeanChristophe,
Shvarev Yuri,
Lagercrantz Hugo,
Perlmann Thomas,
Herlenius Eric
Publication year - 2004
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2003.058560
Subject(s) - respiratory system , respiratory center , biology , hypoxia (environmental) , midbrain , endocrinology , control of respiration , brainstem , medicine , central nervous system , neuroscience , chemistry , organic chemistry , oxygen
Nurr1, a transcription factor belonging to the family of nuclear receptors, is expressed at high levels immediately after birth. Gene‐targeted mice lacking Nurr1 fail to develop midbrain dopaminergic neurones and do not survive beyond 24 h after birth. Dopamine (DA) levels may be regulated by Nurr1, and as DA is involved in both central and peripheral respiratory control, we hypothesized that lack of Nurr1 may impair breathing and cause death by respiratory failure. We demonstrate herein that Nurr1 newborn knockout mice have a severely disturbed breathing pattern characterized by hypoventilation, numerous apnoeas and failure to increase breathing when challenged with hypoxia. In heterozygote Nurr1 mice the response to hypoxia is also altered. Furthermore, the central respiratory rhythm, generated from isolated brainstem–spinal cord preparations, exhibits impaired response to hypoxia in mice lacking Nurr1. Moreover, Nurr1 is expressed in several respiratory‐related regions of the nervous system, including the nucleus of the solitary tract, the nucleus ambiguus and the dorsal motor nucleus of the vagus nerve, and in the carotid bodies. The prominent Nurr1 expression in these areas, involved in respiratory control, along with the severe respiratory phenotype, indicates that Nurr1 plays a major role in the extrauterine adaption of respiratory control and the response to hypoxia.