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Molecular mechanisms underlying‘tying up’ in horses

C. A. Maile, J. R. Hingst, K. K. Mahalingan, A. O. O'Reilly,

M. E. Cleasby, J. R. Mickelson and others

‘TYING UP’, also known as type 1 polysaccharide storage myopathy (PSSM1), is a common condition that damages equine muscle tissue. An inherited skeletal muscle disorder, it is caused by a missense dominant mutation in the equine GYS1 gene associated with increased glycogen synthase (GS) enzyme activity in muscle from affected horses. The disease is histopathologically characterised by increased amylopectate and glycogen accumulation in skeletal muscle fibres; however, the mechanism by which the mutation results in increased GS activity is unknown.

In this study, the authors investigated GS regulation using computer modelling, biochemical analysis of whole muscle extracts and recombinant expressed enzyme kinetics.

Muscle samples were collected by open biopsy under local anaesthesia from the muscle of 12 homozygous normal (RR), 13 heterozygote (HR) and four homozygous mutant (HH) Belgian and Percheron draught horses. Equine muscle biochemical and recombinant enzyme kinetic assays and computer homology modelling were carried out to determine whether higher GS activity in affected horse muscle …

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