title: RET proto-oncogene is important for the development of respiratory CO2 sensitivity.
abstract: Brain stem muscarinic cholinergic pathways are important in respiratory carbon dioxide (CO2) chemosensitivity. Defects in the muscarinic system have been reported in children with congenital/developmental disorders of respiratory control such as sudden infant death syndrome (SIDS) and congenital central hypoventilation syndrome (CCHS). This early onset of disease suggests a possible genetic basis. The muscarinic system is part of the autonomic nervous system which develops from the neural crest. Ret proto-oncogene is important for this development. Thus, a potential role for ret in the development of respiratory CO2 chemosensitivity was considered. Using plethysmography, we assessed the ventilatory response to inhaled CO2 in the unanesthetized offsprings of ret +/- mice. Fractional increases in minute ventilation during hypercapnia relative to isocapnia were 5.1 +/- 3.2, 3.0 +/- 1.6 and 1.4 +/- 0.8 for the ret +/+, ret +/- and ret +/- mice, respectively. The ret knockout mice have a depressed ventilatory response to inhaled CO2. Therefore, the ret gene is an important factor in the pathway of neuronal development which allow respiratory CO2 chemosensitivity.
authors.affiliation: Pulmonary Critical Care Unit, Massachusetts General Hospital, Boston, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Burton
authors.forename: A
authors.initials: A
authors.lastname: Kawashima
authors.forename: J A
authors.initials: JA
authors.lastname: Brayer
authors.forename: H
authors.initials: H
authors.lastname: Kazemi
authors.forename: D C
authors.initials: DC
authors.lastname: Shannon
authors.forename: A
authors.initials: A
authors.lastname: Schuchardt
authors.forename: F
authors.initials: F
authors.lastname: Costantini
authors.forename: V
authors.initials: V
authors.lastname: Pachnis
authors.forename: T B
authors.initials: TB
authors.lastname: Kinane
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001341:Autonomic Nervous System / Q000502:physiology; D002245:Carbon Dioxide / Q000502:physiology*; D002628:Chemoreceptor Cells / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D012119:Respiration / Q000502:physiology*
chemical_list: D011518:Proto-Oncogene Proteins; D002245:Carbon Dioxide