Genetic Galactocerebrosidase Deficiency (Globoid Cell Leukodystrophy, Krabbe Disease) in Rhesus Monkeys (Macaca mulatta)
Abstract:Globoid cell leukodystrophy, or Krabbe disease, is a severe disorder of the peripheral and central nervous system myelin caused by deficient galactocerebrosidase (GALC) activity. This autosomal recessive disease affects humans and animals including dogs, mice, and rhesus monkeys. Cloning of the human and animal GALC genes opened opportunities for therapeutic trials using animal models. We describe the clinical, pathologic, and biochemical features of the affected rhesus monkey. Affected monkeys had very low GALC activity and a two base pair deletion in both copies of the GALC gene. Clinical signs of tremors, hypertonia, and incoordination led to humane euthanasia by 5 months of age. At necropsy, peripheral nerves were enlarged. Microscopically, the cerebral, cerebellar, and spinal cord white matter was infiltrated with periodic acid-Schiff-positive multinucleated globoid cells, and there was a striking lack of myelin. Peripheral nerve fibers were decreased in number and separated by Alcian blue- and safranin O-positive material. Myelin sheaths were greatly diminished. Lipid analysis of brains of 12-day-old and 158-day-old affected monkeys revealed a great excess of psychosine in white matter. The rhesus monkey model will be especially useful for exploring treatment options, including prenatal bone marrow transplantation and various approaches to gene therapy.
Document Type: Research Article
Affiliations: 1: Departments of Pathology and Veterinary Science, Tulane Regional Primate Research Center, Covington, Louisiana, Tulane Regional Primate Research Center, Tulane University, 18703 Three Rivers Rd., Covington, LA 70433 2: Departments of Pathology and Veterinary Science, Tulane Regional Primate Research Center, Covington, Louisiana 3: Department of Neurology, Louisiana State University School of Medicine, New Orleans, Louisiana 4: INSERM-CNRS 189, Lyon-Sud Medical School, and Fondation GilletMerieux, Lyon-Sud Hospital, Pierre Benite, France 5: Departments of Medicine (Medical Genetics) and Biochemistry and Molecular Pharmacology, Jefferson Medical College, Philadelphia, Pennsylvania
Publication date: 1998-10-01
Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.
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