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

Georg M. Stettner, Carlo Viscomi, Massimo Zeviani, Ekkehard Wilichowski, Mathias Dutschmann

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)413-420
Number of pages8
JournalMitochondrion
Volume11
Issue number3
DOIs
Publication statusPublished - May 2011

Keywords

  • Brainstem
  • Ca homeostasis
  • Chemosensitivity
  • COX deficiency
  • Hyperventilation
  • Hypoxia
  • Leigh syndrome
  • Mitochondria
  • Respiratory rhythm
  • Surf1 gene

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Molecular Medicine

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