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

Academic Article


  • 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 In

  • Nature Genetics  Journal
  • Digital Object Identifier (doi)

    Author List

  • Pennacchio LA; Bouley DM; Higgins KM; Scott MP; Noebels JL; Myers RM
  • Start Page

  • 251
  • End Page

  • 258
  • Volume

  • 20
  • Issue

  • 3