Journal article

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

MITOCHONDRION | ELSEVIER SCI LTD | Published : 2011

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. Com..

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Grants

Awarded by Deutsche Forschungsgemeinschaft (DFG) Research Center for Molecular Physiology of the Brain (CMPB Gottingen, Germany and Telethon-Italy)


Funding Acknowledgements

The study was supported by the Deutsche Forschungsgemeinschaft (DFG) Research Center for Molecular Physiology of the Brain (CMPB Gottingen, Germany and Telethon-Italy (Grant No. GGP07019). Neither the CMPB Gottingen nor Telethon-Italy had any involvement in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. The authors thank A.M. Bischoff for excellent technical assistance, Dr. L. Becker and Prof. T. Klopstock (German Mouse Clinic at the German Research Center for Environmental Health (Helmholtz Zentrum), Munich, Germany) for breeding and genotyping the Surf1<SUP>-/-</SUP> KO mice and WT littermates, and Prof. L. Kubin for critical reading of the manuscript.