Nature Neuroscience
6, 1091 - 1100 (2003)
Published online: 25 September 2003; | doi:10.1038/nn1129
MafB deficiency causes defective respiratory rhythmogenesis and fatal central apnea at birthBruno Blanchi1, 6, Louise M Kelly1, 5, 6, Jean-Charles Viemari2, 6, Isabelle Lafon1, Henri Burnet2, Michelle Bévengut2, Silke Tillmanns1, Laurent Daniel3, Thomas Graf4, Gerard Hilaire2
& Michael H Sieweke11
Centre d'Immunologie de Marseille-Luminy, CNRS-INSERM−Université Mediterrané, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. 2
Groupe d'Etude des Réseaux Moteurs, FRE CNRS 2102, 280 Boulevard Ste-Marguerite, 13009 Marseille, France. 3
Laboratoire de Pathologie Nerveuse et Musculaire, IBDM, Faculté de Médecine Timone, 13005 Marseille, France. 4
Albert Einstein College of Medicine, Chanin 302b, 1300 Morris Park Avenue, Bronx, New York 10461, USA. 5
Present address: Harvard Institutes of Medicine, 77 Louis Pasteur Avenue, Boston, Massachusetts 02115, USA. 6
These authors contributed equally to this work.
Correspondence should be addressed to Michael H Sieweke sieweke@ciml.univ-mrs.frThe 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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