Globoid cell leukodystrophy in Cairn and West Highland white terriers
| Autor: | Marie T. Vanier, Paola Luzi, David A. Wenger, Teresa Victoria, Mohammad A. Rafi, D F Patterson, M H Haskins, Charles H. Vite |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Pathology
medicine.medical_specialty Genotype biology.animal_breed Transfection White matter Mice Myelin Dogs Cairn terrier Genetics medicine Animals Humans Dog Diseases Molecular Biology Cells Cultured Genetics (clinical) Brain Chemistry biology Galactocerebrosidase Leukodystrophy Fibroblasts medicine.disease Lipids Magnetic Resonance Imaging Hypotonia Leukodystrophy Globoid Cell medicine.anatomical_structure Krabbe disease Bone marrow medicine.symptom Galactosylceramidase Biotechnology |
| Zdroj: | Journal of Heredity. 90:138-142 |
| DOI: | 10.1093/jhered/90.1.138 |
| Popis: | Krabbe disease or globoid cell leukodystrophy (GLD) is an autosomal recessive disorder resulting from the defective lysosomal hydrolysis of specific galactolipids found primarily in myelin. This leads to severe neurological symptoms including seizures, hypotonia, blindness, and death, usually before 2 years of age in human patients. In addition to human patients, several animals, including dog, mouse, and monkey, have the same disease caused by a deficiency of galactocerebrosidase (GALC) activity. In this article we describe studies in cairn and West Highland white terriers (WHWT) affected with GLD. Through a screening test based on the molecular defect found in these breeds, over 50 cairn terrier carriers have been identified and a colony of five carrier dogs has been established. Affected dogs from this colony plus an affected WHWT were available for study. An affected WHWT was evaluated by magnetic resonance imaging at 6 and 11 months of age and pronounced changes in the T-2 weighted fast spin-echo images were found. Biochemical and pathological evaluation of the same dog after euthanasia at 12 months of age showed a large accumulation of psychosine in the brain and white matter filled with globoid cells. Some comparisons were made to younger affected and carrier dogs. Studies have shown successful transduction of cultured skin fibroblasts from an affected dog and normal canine bone marrow using a retroviral vector containing the human GALC cDNA. Successful treatment of this canine model will lead to studies in some humans with GLD. |
| Databáze: | OpenAIRE |
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