The Studies on Cystatin B Deficient Mice: Neurochemical and Behavioural Alterations in Animal Model of Progressive Myoclonus Epilepsy of Unverricht-lundborg Type
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چکیده
Progressive myoclonus epilepsy of the Unverricht–Lundborg type is a raredisorder associated with mutations in gene encoding the cystatin B, an inhibitorof cysteine proteases. Cystatin B knockout mice share phenotype with humandisease demonstrating similarly the myoclonic seizures, progressive ataxia andneuronal atrophy in hippocampus and cerebellum. We used liquid chromatographic and real time PCR techniques to determine whether glutamateand GABA content as well as vesicular glutamate transporter 1, vesicularGABA transporter 1 and glutamic acid decarboxylase (GAD65) gene expression levels are disturbed in mutant mice brain. We found the significant decrease in glutamate content and vesicular glutamate transporter 1 geneexpression levels as well as the increase in GAD65 expression levels while theGABA transporter gene and GABA concentrations remain unchanged in
منابع مشابه
Neuropathological changes in a mouse model of progressive myoclonus epilepsy: cystatin B deficiency and Unverricht-Lundborg disease.
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 EPMI in humans. To provide further insight in...
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Two mutations in the cystatin B gene, a 3' splice mutation and a stop codon mutation, were previously found in patients with progressive myoclonus epilepsy of Unverricht-Lundborg type [Pennacchio et al. (1996): Science 271:1731-1734]. We present here a new mutation 2404deltaTC: a 2-bp deletion within the third exon of the cystatin B gene in an Unverricht-Lundborg patient. This mutation results ...
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The inherited epilepsy Unverricht-Lundborg disease (EPM1) is caused by loss-of-function mutations in the cysteine protease inhibitor, cystatin B. Because cystatin B inhibits a class of lysosomal cysteine proteases called cathepsins, we hypothesized that increased proteolysis by one or more of these cathepsins is likely to be responsible for the seizure, ataxia, and neuronal apoptosis phenotypes...
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Unverricht-Lundborg type progressive myoclonus epilepsy (EPM1, OMIM 254800) is an autosomal recessive disorder characterized by onset at the age of 6 to 16 years, incapacitating stimulus-sensitive myoclonus and tonic-clonic epileptic seizures. It is caused by mutations in the gene encoding cystatin B. Previously, widespread white matter changes and atrophy has been detected both in adult EPM1 p...
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Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1) is an autosomal recessively inherited neurodegenerative disease, manifesting with myoclonus, seizures and ataxia, caused by mutations in the cystatin B (CSTB) gene. With the aim of understanding the molecular basis of pathogenetic events in EPM1 we characterized gene expression changes in the cerebella of pre-symptomatic postnata...
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