Nature Genetics
20, 251 - 258 (1998)
doi:10.1038/3059
Progressive ataxia, myoclonic epilepsy and cerebellar apoptosis in cystatin
B-deficient miceLen A. Pennacchio1, 2, Donna M. Bouley3, Kay M. Higgins4, 5, Matthew P. Scott2, 4, 5, Jeffrey L. Noebels6
& Richard M. Myers21
Department of Biological Sciences, Stanford University
School of Medicine, Stanford, California 94305-5120, USA
2
Department of Genetics, Stanford University School
of Medicine, Stanford, California 94305-5120, USA
3
Department of Comparative Medicine, Stanford University
School of Medicine, Stanford, California 94305-5120, USA
4
Department of Developmental Biology, Stanford University
School of Medicine, Stanford, California 94305-5120, USA
5
Howard Hughes Medical Institute, Stanford University
School of Medicine, Stanford, California 94305-5120, USA. 6
Departments of Neurology, and Molecular and Human Genetics,
Baylor College of Medicine, One Baylor Plaza,
Houston, Texas 77030, USA.
Correspondence should be addressed to Richard M. Myers myers@shgc.stanford.eduLoss-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.
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