title: Canine spongiform leukoencephalomyelopathy is associated with a missense mutation in cytochrome b.
abstract: 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. NC002008 ) that results in an amino acid change of valine-98 to methionine (V98M) of mitochondrial encoded cytochrome b. Western blot analysis showed increased levels of core I and core II but decreased level of cytochrome c1 of the complex III and cytochrome c oxidase of the complex IV of the respiratory chain.
authors: Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA. lif@svm.vetmed.wisc.edu
authors: Fang-Yuan
authors: FY
authors: Li
authors: Paul A
authors: PA
authors: Cuddon
authors: Jonathan
authors: J
authors: Song
authors: Sheri L
authors: SL
authors: Wood
authors: Jon S
authors: JS
authors: Patterson
authors: G Diane
authors: GD
authors: Shelton
authors: Ian D
authors: ID
authors: Duncan
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000134:cerebrospinal fluid; D000090:Acetoacetates / Q000134:cerebrospinal fluid; D000818:Animals; D015153:Blotting, Western; D017825:Canavan Disease / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000473:pathology; D045303:Cytochromes b / Q000235:genetics*; D003575:Cytochromes c1 / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics; D004283:Dog Diseases / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000473:pathology; D004285:Dogs; D014450:Electron Transport Complex III / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D020271:Heredodegenerative Disorders, Nervous System / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D010375:Pedigree
chemical_list: D000090:Acetoacetates; D004272:DNA, Mitochondrial; C016635:acetoacetic acid; D045303:Cytochromes b; D003575:Cytochromes c1; D003576:Electron Transport Complex IV; D014450:Electron Transport Complex III; D020155:3-Hydroxybutyric Acid