The molecular mechanisms that underpin a common genetic form of “tying up” in horses have been discovered by RVC scientists.

Scientifically known as type one polysaccharide storage myopathy (PSSM1), tying up is a common condition that damages equine muscle tissue.

Richard and Charlotte
Professor Richard Piercy and Dr Charlotte Maile led the international team of scientists who took part in the research.

The genetic cause of PSSM1 was discovered at the University of Minnesota in 2008, when researchers found affected animals have a mutation of a key enzyme (glycogen synthase) involved in energy metabolism in muscle and increased storage of glycogen and an abnormal type of polysaccharide (a form of carbohydrate).

Horses carrying the mutation are prone to tying up and other muscle problems, such as weakness.

Mutant hyperactivity

Until now, however, nobody knew the precise mechanism by which the mutation caused increased enzyme activity in muscles.

According to the RVC’s latest findings, the mutation in the enzyme leads to a change in the enzyme’s structure, which leaves it permanently active, so it cannot be “switched off”. This hyperactivity of mutant equine enzyme explains the increased muscle glycogen and the accumulation of polysaccharide that leads to the clinical problems in affected horses.

The college’s discovery, will, it said, enable the team to work towards improved treatments and management for the disorder, while improving the welfare of affected horses.

Targeted approaches

Richard Piercy, professor of comparative neuromuscular disease at the RVC, said: “Managing horses that tie up is hard, and some recommended treatments work poorly in some animals.

“By revealing the precise mechanism for this form of tying up, our work should make a real difference. Our hope is, by targeting specific approaches to the problem – rather than a ‘one treatment fits all’ – horse welfare will be improved, allowing them to get back to exercise, which has to be good for the horse and its owner.”

An international team of scientists took part in the research, led by Charlotte Maile and Prof Piercy. Contributors hailed from the University of Copenhagen, University of Minnesota, Indiana University School of Medicine and Liverpool John Moores University.

The RVC’s work was partly funded by the Petplan Charitable Trust and Morris Animal Foundation.

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