Progressive ataxia, myoclonic epilepsy and cerebellar apoptosis in cystatin B-deficient mice.

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.

• Authors: L A Pennacchio, D M Bouley, K M Higgins, M P Scott, J L Noebels, R M Myers
• Journal: Nature genetics (Nat Genet) Vol. 20 Issue 3 Pg. 251-8 (Nov 1998) ISSN: 1061-4036 [Print] United States
• PMID: 9806543 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• CSTB protein, human
• Cstb protein, mouse
• Cystatins
• Cysteine Proteinase Inhibitors
• DNA Primers
• Cystatin B

Topics

• Amino Acid Sequence
• Animals
• Apoptosis (genetics)
• Ataxia (genetics, pathology)
• Base Sequence
• Cerebellum (pathology)
• Corneal Opacity (genetics)
• Cystatin B
• Cystatins (deficiency, genetics, physiology)
• Cysteine Proteinase Inhibitors (deficiency, genetics, physiology)
• DNA Primers (genetics)
• Disease Models, Animal
• Epilepsies, Myoclonic (genetics, pathology)
• Female
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Inbred CBA
• Mice, Knockout
• Models, Genetic
• Mutation
• Phenotype