The molecular mechanism that underpins a common form of “tying up” has been identified by an international team of researchers.
Type 1 Polysaccharide Storage Myopathy (PSSM1) particularly affects Quarter horses and draught breeds.
The genetic cause of the disease was discovered in 2008 by researchers at the University of Minnesota, who found that affected animals have a mutation of a key enzyme (glycogen synthase) which is involved in energy metabolism. This leads to increased storage of glycogen and an abnormal type of polysaccharide, a form of carbohydrate. The mutation is inherited in dominant fashion – which means that only one copy of the gene needs to be inherited to cause the disease.
Until now, no-
They found that the mutation 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. A full report of the research is published in the journal Biochimica et Biophysica Acta.
This breakthrough in the understanding of PSSM1 might lead to the development of novel treatments for this debilitating disease. It helps explain why some forms of treatment might be ineffective. RVC researchers are now working towards improved treatments and management of this disorder.
“PSSM1 is a very common disease, especially in some breeds. Finally, we know the reason why these horses store excessive glycogen and polysaccharide in their muscles,” Maile said.
“Our goal now is to use this information in designing new treatments and management strategies.”
Piercy said that managing horses who tie-
“By revealing the precise mechanism for this form of tying up, our work should make a real difference. Our hope is that by targeting specific approaches to the problem, –
The work was partly funded by the Petplan Charitable Trust and the Morris Animal Foundation.
A highly prevalent equine glycogen storage disease is explained by constitutive activation of a mutant glycogen synthase. Maile CA, Hingst JR, Mahalingan KK, O’Reilly AO, Cleasby ME, Mickelson JR, McCue ME, Anderson SM, Hurley TD, Wojtaszewski JF, Piercy RJ. Biochim Biophys Acta. (2016). doi: 10.1016/j.bbagen.2016.08.021