title: Genes modulating chemical breathing control: lessons from mutant animals.
abstract: Genetic factors influence breathing control. Respiratory phenotypes of mutant mice may help to better understand these factors. Congenital central hypoventilation syndrome (CCHS) is a rare disorder defined as failure of chemical control of breathing causing central alveolar hypoventilation, especially during sleep. A genetic basis for CCHS is supported by several arguments, mainly the identification, in a few CCHS patients, of heterozygous mutations of genes contributing to neural crest cell development, namely, genes involved in the endothelin and c-ret pathways. Furthermore, plethysmography studies of the respiratory phenotypes of newborn heterozygous mutant mice have shown that genes in both pathways are involved in breathing control at birth. Nevertheless, no single gene mutation in newborn mice reproduces the human CCHS phenotype. Avenues for future research into the genetics of CCHS include (i) testing of mutant newborn mice for genes in other pathways and (ii) use of microarrays to identify gene clusters that should be associated with abnormal chemical breathing control.
authors.affiliation: Laboratoire de Neurologie et Physiologie du Développement, INSERM E9935, Hôpital Robert-Debré, 48 Boulevard Sérurier, 75019 Paris, France. claude.gaultier@rdb.ap-hop-paris.fr
authors.forename: Claude
authors.initials: C
authors.lastname: Gaultier
authors.forename: Stéphane
authors.initials: S
authors.lastname: Dauger
authors.forename: Michel
authors.initials: M
authors.lastname: Simonneau
authors.forename: Jorge
authors.initials: J
authors.lastname: Gallego
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000502:physiology; D004195:Disease Models, Animal; D016232:Endothelins / Q000502:physiology; D005821:Genetic Techniques; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D009432:Neural Crest / Q000196:embryology / Q000502:physiology; D010641:Phenotype; D012119:Respiration / Q000235:genetics*; D020182:Sleep Apnea, Central / Q000235:genetics* / Q000503:physiopathology
chemical_list: D016232:Endothelins