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

Nat Genet. 1998 Nov;20(3):251-8. doi: 10.1038/3059.


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

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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


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