Neuropathological changes in a mouse model of progressive myoclonus epilepsy: Cystatin B deficiency and Unverricht-Lundborg disease

Patrick Shannon, Len A. Pennacchio, Megan K. Houseweart, Berge A. Minassian, Richard M. Myers

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


Progressive myoclonus epilepsy of the Unverricht-Lundborg type (EPM1) is a recessively inherited neurodegenerative disease caused by loss-of-function mutations in the gene encoding cystatin B, a cysteine protease inhibitor. Mice with disruptions in this gene display myoclonic seizures, progressive ataxia, and cerebellar pathology closely paralleling EPM1 in humans. To provide further insight into our understanding of EPM1, we report pathological findings in brains from cystatin B-deficient mice. In addition to confirming the loss of cerebellar granular cell neurons by apoptosis, we identified additional neuronal apoptosis in young mutant mice (3-4 months old) within the hippocampal formation and entorhinal cortex. In older mutant mice (16-18 months old), there was also gliosis most marked in the presubiculum and parasubiculum of the hippocampal formation, as well as the entorhinal cortex, neocortex, and striatum. Furthermore, widespread white matter gliosis was also noted, which may be a secondary phenomenon. Within the cerebral cortex, cellular atrophy was a prominent finding in the superficial neurons of the prosubiculum. Finally, we show that mutant mice in either a "seizure-prone" or "seizure-resistant" genetic background display similar neuropathological changes. These findings indicate that neuronal atrophy is an important consequence of cystatin-B deficiency independent of seizure events, suggesting a physiological role for this protein in the maintenance of normal neuronal structure.

Original languageEnglish (US)
Pages (from-to)1085-1091
Number of pages7
JournalJournal of neuropathology and experimental neurology
Issue number12
StatePublished - Dec 1 2002


  • Cystatin B
  • EPM1
  • Neuropathology
  • Progressive myoclonus epilepsy
  • Protease inhibitor
  • Unverricht-Lundborg disease

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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