title: Hypoxic and hypercapnic challenges unveil respiratory vulnerability of Surf1 knockout mice, an animal model of Leigh syndrome.
abstract: Surf1 gene mutations were detected as a main cause for Leigh syndrome (LS), also known as infantile subacute necrotizing encephalomyelopathy. This syndrome which is commonly associated with systemic cytochrome c oxidase (COX) deficiency manifests in early childhood and has an invariable poor prognosis. Progressive disturbances of the respiratory function, for which both the metabolic condition and necrotizing brainstem lesions contribute, belong to the major symptoms of LS. A constitutive knockout (KO) mouse for Surf1 enables invasive investigations of distinct aspects of LS. In the present study the respiratory function was analyzed applying an arterially perfused brainstem preparation. Compared to wild type (WT) preparations Surf1 KO preparations had a higher baseline respiratory frequency and abnormal responses to hypoxia and hypercapnia that involved both respiratory frequency and motor nerve discharge pattern. These data suggest that COX deficiency impairs peripheral and/or central chemoreceptor function.
authors.affiliation: Department of Pediatrics and Pediatric Neurology, University Medicine Göttingen, Georg August University, Robert-Koch-Str. 40, 37075 Göttingen, Germany. stettner@vet.upenn.edu
authors.forename: Georg M
authors.initials: GM
authors.lastname: Stettner
authors.forename: Carlo
authors.initials: C
authors.lastname: Viscomi
authors.forename: Massimo
authors.initials: M
authors.lastname: Zeviani
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Wilichowski
authors.forename: Mathias
authors.initials: M
authors.lastname: Dutschmann
mesh_terms: D000818:Animals; D002628:Chemoreceptor Cells / Q000502:physiology; D006801:Humans; D006935:Hypercapnia / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D007888:Leigh Disease / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D023421:Models, Animal; D056152:Respiratory Rate
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C092928:Surf-1 protein