Glycogen metabolism in tissues from a mouse model of Lafora disease

Wei Wang, Hannes Lohi, Alexander V. Skurat, Anna A. DePaoli-Roach, Berge A. Minassian, Peter J. Roach

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Laforin, encoded by the EPM2A gene, by sequence is a member of the dual specificity protein phosphatase family. Mutations in the EPM2A gene account for around half of the cases of Lafora disease, an autosomal recessive neurodegenerative disorder, characterized by progressive myoclonus epilepsy. The hallmark of the disease is the presence of Lafora bodies, which contain polyglucosan, a poorly branched form of glycogen, in neurons, muscle and other tissues. Glycogen metabolizing enzymes were analyzed in a transgenic mouse over-expressing a dominant negative form of laforin that accumulates Lafora bodies in several tissues. Skeletal muscle glycogen was increased 2-fold as was the total glycogen synthase protein. However, the -/+glucose-6-P activity of glycogen synthase was decreased from 0.29 to 0.16. Branching enzyme activity was increased by 30%. Glycogen phosphorylase activity was unchanged. In whole brain, no differences in glycogen synthase or branching enzyme activities were found. Although there were significant differences in enzyme activities in muscle, the results do not support the hypothesis that Lafora body formation is caused by a major change in the balance between glycogen elongation and branching activities.

Original languageEnglish (US)
Pages (from-to)264-269
Number of pages6
JournalArchives of Biochemistry and Biophysics
Volume457
Issue number2
DOIs
StatePublished - Jan 15 2007

Fingerprint

Lafora Disease
Glycogen
Metabolism
Glycogen Synthase
Enzyme activity
1,4-alpha-Glucan Branching Enzyme
Tissue
Muscle
Genes
Dual-Specificity Phosphatases
Progressive Myoclonic Epilepsy
Glycogen Phosphorylase
Muscles
Phosphoprotein Phosphatases
Enzymes
Neurodegenerative Diseases
Transgenic Mice
Neurons
Elongation
Brain

Keywords

  • Branching enzyme
  • Dual specificity phosphatase
  • Glycogen
  • Glycogen synthase
  • Glycogen synthase kinase-3
  • Lafora disease
  • Laforin

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Glycogen metabolism in tissues from a mouse model of Lafora disease. / Wang, Wei; Lohi, Hannes; Skurat, Alexander V.; DePaoli-Roach, Anna A.; Minassian, Berge A.; Roach, Peter J.

In: Archives of Biochemistry and Biophysics, Vol. 457, No. 2, 15.01.2007, p. 264-269.

Research output: Contribution to journalArticle

Wang, Wei ; Lohi, Hannes ; Skurat, Alexander V. ; DePaoli-Roach, Anna A. ; Minassian, Berge A. ; Roach, Peter J. / Glycogen metabolism in tissues from a mouse model of Lafora disease. In: Archives of Biochemistry and Biophysics. 2007 ; Vol. 457, No. 2. pp. 264-269.
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