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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Apoptosis / genetics*
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Ataxia / genetics*
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Ataxia / pathology
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Base Sequence
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Cerebellum / pathology*
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Corneal Opacity / genetics
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Cystatin B
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Cystatins / deficiency*
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Cystatins / genetics*
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Cystatins / physiology
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Cysteine Proteinase Inhibitors / deficiency*
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Cysteine Proteinase Inhibitors / genetics*
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Cysteine Proteinase Inhibitors / physiology
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DNA Primers / genetics
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Disease Models, Animal
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Epilepsies, Myoclonic / genetics*
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Epilepsies, Myoclonic / pathology
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Female
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Humans
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Inbred CBA
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Mice, Knockout
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Models, Genetic
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Mutation
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Phenotype
Substances
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CSTB protein, human
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Cstb protein, mouse
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Cystatins
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Cysteine Proteinase Inhibitors
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DNA Primers
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Cystatin B