A highly prevalent equine glycogen storage disease is explained by constitutive activation of a mutant glycogen synthase.

ABSTRACT:

Background

Equine type 1 polysaccharide storage myopathy (PSSM1) is associated with a missense mutation (R309H) in the glycogen synthase (GYS1) gene, enhanced glycogen synthase (GS) activity and excessive glycogen and amylopectate inclusions in muscle.

Methods

Equine muscle biochemical and recombinant enzyme kinetic assays in vitro and homology modelling in silico, were used to investigate the hypothesis that higher GS activity in affected horse muscle is caused by higher GS expression, dysregulation, or constitutive activation via a conformational change.

Results

PSSM1-affected horse muscle had significantly higher glycogen content than control horse muscle despite no difference in GS expression. GS activity was significantly higher in muscle from homozygous mutants

SUBMITTER: Maile CA 

PROVIDER: S-EPMC5148651 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature