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Leigh-like subacute necrotising encephalopathy in Yorkshire Terriers: neuropathological characterisation, respiratory chain activities and mitochondrial DNA

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Abstract

Our knowledge of molecular mechanisms underlying mitochondrial disorders in humans has increased considerably during the past two decades. Mitochondrial encephalomyopathies have sporadically been reported in dogs. However, molecular and biochemical data that would lend credence to the suspected mitochondrial origin are largely missing. This study was aimed to characterise a Leigh-like subacute necrotising encephalopathy (SNE) in Yorkshire Terriers and to shed light on its enzymatic and genetic background. The possible resemblance to SNE in Alaskan Huskies and to human Leigh syndrome (LS) was another focus of interest. Eleven terriers with imaging and/or gross evidence of V-shaped, non-contiguous, cyst-like cavitations in the striatum, thalamus and brain stem were included. Neuropathological examinations focussed on muscle, brain pathology and mitochondrial ultrastructure. Further investigations encompassed respiratory-chain activities and the mitochondrial DNA. In contrast to mild non-specific muscle findings, brain pathology featured the stereotypic triad of necrotising grey matter lesions with relative preservation of neurons in the aforementioned regions, multiple cerebral infarcts, and severe patchy Purkinje-cell degeneration in the cerebellar vermis. Two dogs revealed a reduced activity of respiratory-chain-complexes I and IV. Genetic analyses obtained a neutral tRNA-LeuUUR A-G-transition only. Neuropathologically, SNE in Yorkshire Terriers is nearly identical to the Alaskan Husky form and very similar to human LS. This study, for the first time, demonstrated that canine SNE can be associated with a combined respiratory chain defect. Mitochondrial tRNA mutations and large genetic rearrangements were excluded as underlying aetiology. Further studies, amongst relevant candidates, should focus on nuclear encoded transcription and translation factors.

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Acknowledgments

We thank Bettina Treske and Karin Stingl for excellent technical assistance. This work was supported by the Deutsche Forschungsgesellschaft to M.F·B. (Ba1438/3 and 4) and to S·H. (Ho2374/1-1).

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Authors and Affiliations

  1. Chair of General Pathology and Neuropathology, Institute of Veterinary Pathology, Ludwig-Maximilians University of Munich, Munich, Germany

    Kerstin Baiker, Wolfgang Schmahl & Kaspar Matiasek

  2. Institute of Microbiology & Laboratory Diagnostics, Gauting, Germany

    Sabine Hofmann

  3. Section of Neurology, Small Animal Medical Clinic, Ludwig-Maximilians University of Munich, Munich, Germany

    Andrea Fischer

  4. Small Animal Referral Practice, Piding, Germany

    Thomas Gödde

  5. Small Animal Referral Clinic, Babenhausen, Germany

    Susanne Medl

  6. Institute of Clinical Chemistry and Molecular Diagnostics, Ludwigshafen City Hospital, Ludwigshafen, Germany

    Matthias F. Bauer

  7. Neuropathology Laboratory, The Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk, CB8 7UU, UK

    Kaspar Matiasek

Authors
  1. Kerstin Baiker
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  2. Sabine Hofmann
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  3. Andrea Fischer
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  4. Thomas Gödde
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  5. Susanne Medl
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  6. Wolfgang Schmahl
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  7. Matthias F. Bauer
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  8. Kaspar Matiasek
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Corresponding author

Correspondence to Kaspar Matiasek.

Additional information

S. Hofmann and M. F. Bauer contributed equally.

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Baiker, K., Hofmann, S., Fischer, A. et al. Leigh-like subacute necrotising encephalopathy in Yorkshire Terriers: neuropathological characterisation, respiratory chain activities and mitochondrial DNA. Acta Neuropathol 118, 697–709 (2009). https://doi.org/10.1007/s00401-009-0548-6

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  • DOI: https://doi.org/10.1007/s00401-009-0548-6

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