Hypoxic and hypercapnic challenges unveil respiratory vulnerability of Surf1 knockout mice, an animal model of Leigh syndrome.

TitleHypoxic and hypercapnic challenges unveil respiratory vulnerability of Surf1 knockout mice, an animal model of Leigh syndrome.
Publication TypeJournal Article
Year of Publication2011
AuthorsStettner, GM, Viscomi, C, Zeviani, M, Wilichowski, E, Dutschmann, M
JournalMitochondrion
Volume11
Issue3
Pagination413-20
Date Published2011 May
ISSN1872-8278
KeywordsAnimals, Chemoreceptor Cells, Humans, Hypercapnia, Hypoxia, Leigh Disease, Male, Membrane Proteins, Mice, Mice, Knockout, Mitochondrial Proteins, Models, Animal, Respiratory Rate
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.

DOI10.1016/j.mito.2010.12.011
Alternate JournalMitochondrion
Citation Key10.1016/j.mito.2010.12.011
PubMed ID21167962
Grant ListGGP07019 / / Telethon / Italy
GTF07004 / / Telethon / Italy