Progressive ataxia, myoclonic epilepsy and cerebellar apoptosis in cystatin B-deficient mice.
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.
Pubmed ID: 9806543 RIS Download
Amino Acid Sequence | Animals | Apoptosis | Ataxia | Base Sequence | Cerebellum | Corneal Opacity | Cystatin B | Cystatins | Cysteine Proteinase Inhibitors | DNA Primers | Disease Models, Animal | Epilepsies, Myoclonic | Female | Humans | Male | Mice | Mice, Inbred C57BL | Mice, Inbred CBA | Mice, Knockout | Models, Genetic | Mutation | Phenotype