Abstract |
The genetic basis for the development of brainstem neurons that generate respiratory rhythm is unknown. Here we show that mice deficient for the transcription factor MafB die from central apnea at birth and are defective for respiratory rhythmogenesis in vitro. MafB is expressed in a subpopulation of neurons in the preBötzinger complex (preBötC), a putative principal site of rhythmogenesis. Brainstems from Mafb(-/-) mice are insensitive to preBötC electrolytic lesion or stimulation and modulation of rhythmogenesis by hypoxia or peptidergic input. Furthermore, in Mafb(-/-) mice the preBötC, but not major neuromodulatory groups, presents severe anatomical defects with loss of cellularity. Our results show an essential role of MafB in central respiratory control, possibly involving the specification of rhythmogenic preBötC neurons.
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Authors | Bruno Blanchi, Louise M Kelly, Jean-Charles Viemari, Isabelle Lafon, Henri Burnet, Michelle Bévengut, Silke Tillmanns, Laurent Daniel, Thomas Graf, Gerard Hilaire, Michael H Sieweke |
Journal | Nature neuroscience
(Nat Neurosci)
Vol. 6
Issue 10
Pg. 1091-100
(Oct 2003)
ISSN: 1097-6256 [Print] United States |
PMID | 14513037
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Avian Proteins
- Biomarkers
- DNA-Binding Proteins
- Homeodomain Proteins
- MafB Transcription Factor
- Mafb protein, mouse
- NBPhox protein
- Oncogene Proteins
- Receptors, Neurokinin-1
- Transcription Factors
- Substance P
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Topics |
- Action Potentials
(drug effects, physiology)
- Afferent Pathways
(drug effects, embryology, metabolism)
- Animals
- Animals, Newborn
- Avian Proteins
- Biomarkers
- DNA-Binding Proteins
(deficiency, genetics)
- Disease Models, Animal
- Electric Stimulation
- Fetus
- Homeodomain Proteins
(metabolism)
- MafB Transcription Factor
- Mice
- Mice, Knockout
- Nerve Net
(drug effects, embryology, metabolism)
- Neurons
(drug effects, metabolism, pathology)
- Oncogene Proteins
- Organ Culture Techniques
- Periodicity
- Receptors, Neurokinin-1
(agonists, metabolism)
- Respiration
(drug effects, genetics)
- Respiratory Center
(abnormalities, pathology, physiopathology)
- Sleep Apnea, Central
(genetics, metabolism, physiopathology)
- Substance P
(metabolism, pharmacology)
- Transcription Factors
(deficiency, genetics, metabolism)
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