MafB deficiency causes defective respiratory rhythmogenesis and fatal central apnea at birth

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

doi:10.1038/nn1129

MafB deficiency causes defective respiratory rhythmogenesis and fatal central apnea at birth

Nat Neurosci. 2003 Oct;6(10):1091-100. doi: 10.1038/nn1129.

Authors

Bruno Blanchi¹, Louise M Kelly, Jean-Charles Viemari, Isabelle Lafon, Henri Burnet, Michelle Bévengut, Silke Tillmanns, Laurent Daniel, Thomas Graf, Gerard Hilaire, Michael H Sieweke

Affiliation

¹ Centre d'Immunologie de Marseille-Luminy, CNRS-INSERM-Université Mediterrané, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France.

PMID: 14513037
DOI: 10.1038/nn1129

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Action Potentials / drug effects
Action Potentials / physiology
Afferent Pathways / drug effects
Afferent Pathways / embryology
Afferent Pathways / metabolism
Animals
Animals, Newborn
Avian Proteins*
Biomarkers
DNA-Binding Proteins / deficiency*
DNA-Binding Proteins / genetics
Disease Models, Animal
Electric Stimulation
Fetus
Homeodomain Proteins / metabolism
MafB Transcription Factor
Mice
Mice, Knockout
Nerve Net / drug effects
Nerve Net / embryology
Nerve Net / metabolism
Neurons / drug effects
Neurons / metabolism*
Neurons / pathology
Oncogene Proteins*
Organ Culture Techniques
Periodicity
Receptors, Neurokinin-1 / agonists
Receptors, Neurokinin-1 / metabolism
Respiration / drug effects
Respiration / genetics*
Respiratory Center / abnormalities
Respiratory Center / pathology
Respiratory Center / physiopathology*
Sleep Apnea, Central / genetics*
Sleep Apnea, Central / metabolism
Sleep Apnea, Central / physiopathology
Substance P / metabolism
Substance P / pharmacology
Transcription Factors / deficiency*
Transcription Factors / genetics
Transcription Factors / metabolism

Substances

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