Ventilatory responses to hypercapnia and hypoxia in Mash-1 heterozygous newborn and adult mice

Normal control of breathing is characterized by maintenance of CO2 and O-2 arterial pressures at constant levels by appropriate ventilatory responses to changes in CO2 production and O-2 consumption. Abnormal development of t his regulatory system during embryogenesis may produce early impairments in chemosensitivity, as in congenital central hypoventilation syndrome. The p resent study addresses the role of the mammalian achaetescute homologous ge ne (Mash-l) in the development of respiratory control. We analyzed ventilat ory responses to hypercapnia (8% CO2, 21% O-2, 71% N-2) and hypoxia (10% O- 2, 3% CO2, 87% N-2) in newborn and adult Mash-1 heterozygous mice (Mash-1(/-)) and their wild-type littermates (Mash-1(+/+)). Ventilation, breath dur ation, and tidal volume were measured using whole-body plethysmography. Ven tilatory responses to hypercapnia were significantly weaker in newborn male Mash-(+/-) compared with Mash-1(+/+) mice as a result of a weaker breath-d uration response. No differences were observed between adult Mash-1(+/-) an d Mash-1(+/+) mice. Our data suggest that Mash-1 may be involved in respira tory control development via mechanisms linked to the X chromosome.