Abstract
Normal control of breathing is characterized by maintenance of CO2 and O2 arterial pressures at constant levels by appropriate ventilatory responses to changes in CO2 production and O2 consumption. Abnormal development of this regulatory system during embryogenesis may produce early impairments in chemosensitivity, as in congenital central hypoventilation syndrome. The present study addresses the role of the mammalian achaete-scute homologous gene (Mash-1) in the development of respiratory control. We analyzed ventilatory responses to hypercapnia (8% CO2, 21% O2, 71% N2) and hypoxia (10% O2, 3% CO2, 87% N2) in newborn and adult Mash-1 heterozygous mice (Mash-1+/−) and their wild-type littermates (Mash-1+/+). Ventilation, breath duration, and tidal volume were measured using whole-body plethysmography. Ventilatory responses to hypercapnia were significantly weaker in newborn male Mash-1+/− compared with Mash-1+/+ mice as a result of a weaker breath-duration response. No differences were observed between adult Mash-1+/− and Mash-1+/+ mice. Our data suggest that Mash-1 may be involved in respiratory control development via mechanisms linked to the X chromosome.
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Abbreviations
- CCHS:
-
congenital central hypoventilation syndrome
- Mash-1 :
-
mammalian achaete-scute homologous gene
- ret :
-
rearranged during transfection
- TTOT:
-
breath duration
- VT:
-
tidal volume
- VE:
-
ventilation
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Acknowledgements
The authors thank Dr. François Guillemot, LGCM, Strasbourg, France, for the kind gift of Mash-1+/− founders.
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C.M. and V.N., respectively, were supported by fellowships from Naître et Vivre and Ligue Nationale contre le Cancer. C.M. and S.R were supported by Fondation pour la Recherche Médicale.
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Dauger, S., Renolleau, S., Vardon, G. et al. Ventilatory Responses to Hypercapnia and Hypoxia in Mash-1 Heterozygous Newborn and Adult Mice. Pediatr Res 46, 535 (1999). https://doi.org/10.1203/00006450-199911000-00008
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DOI: https://doi.org/10.1203/00006450-199911000-00008
