Burton, MD; Kawashima, A; Brayer, JA; Kazemi, H; Shannon, DC; Schuchardt, A; Costantini, F; Pachnis, V; Kinane, TB

Journal of the Autonomic Nervous System [J. AUTON. NERV. SYST.], vol. 63, no. 3, pp. 137-143, Apr 1997

Brain stem muscarinic cholinergic pathways are important in respiratory carbon dioxide (CO sub(2)) 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 CO sub(2) chemosensitivity was considered. Using plethysmography, we assessed the ventilatory response to inhaled CO sub(2) in the unanesthetized offsprings of ret super(+/-) mice. Fractional increases in minute ventilation during hypercapnia relative to isocapnia were 5.1 plus or minus 3.2, 3.0 plus or minus 1.6 and 1.4 plus or minus 0.8 for the ret super(+/+), ret super(+/-) and ret super(-/-) mice, respectively. The ret knockout mice have a depressed ventilatory response to inhaled CO sub(2). Therefore, the ret gene is an important factor in the pathway of neuronal development which allow respiratory CO sub(2) chemosensitivity.