Canine spongiform leukoencephalomyelopathy is associated with a missense mutation in cytochrome b

Two families of dogs (Australian cattle dogs and Shetland sheepdogs) with an inherited spongiform leukoencephalomyelopathy were identified, with widespread vacuolation of white matter of the brain and spinal cord. Affected dogs of both breeds developed tremors at 2 -9 weeks of age followed by progressive neurological worsening with ataxia, paresis, paralysis, spasticity, and cranial nerve dysfunction. The modes of inheritance of both families were most likely maternal. The cerebrospinal fluid (CSF) analysis showed elevated ratio of 3-OH butyrate to acetoacetic acid. Mitochondrial DNA sequencing showed a G to A transition at 14,474 nt (G14474A, GenBank accession no. NC(-)002008) that results in an amino acid change of valine-98 to methionine (V98M) of mitoctiondrial encoded cytochrome b. Western blot analysis showed increased levels of core I and core 11 but decreased level of cytochrome c, of the complex III and cytochrome c oxidase of the complex IV of the respiratory chain. (c) 2005 Elsevier Inc. All rights reserved.