1. Progressive ataxia, myoclonic epilepsy and cerebellar apoptosis in cystatin B-deficient mice.
- Author
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Pennacchio LA, Bouley DM, Higgins KM, Scott MP, Noebels JL, and Myers RM
- Subjects
- Amino Acid Sequence, Animals, Ataxia pathology, Base Sequence, Corneal Opacity genetics, Cystatin B, Cystatins physiology, Cysteine Proteinase Inhibitors physiology, DNA Primers genetics, Disease Models, Animal, Epilepsies, Myoclonic pathology, Female, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Inbred CBA, Mice, Knockout, Models, Genetic, Mutation, Phenotype, Apoptosis genetics, Ataxia genetics, Cerebellum pathology, Cystatins deficiency, Cystatins genetics, Cysteine Proteinase Inhibitors deficiency, Cysteine Proteinase Inhibitors genetics, Epilepsies, Myoclonic genetics
- Abstract
Loss-of-function mutations in the gene (CSTB) encoding human cystatin B, a widely expressed cysteine protease inhibitor, are responsible for a severe neurological disorder known as Unverricht-Lundborg disease (EPM1). The primary cellular events and mechanisms underlying the disease are unknown. We found that mice lacking cystatin B develop myoclonic seizures and ataxia, similar to symptoms seen in the human disease. The principal cytopathology appears to be a loss of cerebellar granule cells, which frequently display condensed nuclei, fragmented DNA and other cellular changes characteristic of apoptosis. This mouse model of EPM1 provides evidence that cystatin B, a non-caspase cysteine protease inhibitor, has a role in preventing cerebellar apoptosis.
- Published
- 1998
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