The MYH1 genetic mutation can strike horses in two ways, causing extreme damage to the horse's muscles -- including IMM. Though the mutation is permanent, experts say owners of horses who have it can take steps to minimize risk and quickly treat any disease. • Photo by Molly Montag.

Living With MYH1

For years, horse owners were baffled by seemingly healthy animals whose muscles began to waste away before their eyes. The horses, after contracting strangles or in some cases without any warning at all, lost massive amounts of muscle along their backs, loins or croups.

Other horses suffered severe and extremely painful episodes of muscle cramping — called rhabdomyolysis, commonly referred to as “tying up” — except this occurred without exercise, which is often the trigger for that condition.

Advances in science have linked both of those conditions — immune mediated myositis (IMM), where the body attacks its own muscle and causes severe atrophy; and non-exertional rhabdomyolysis — with a genetic mutation in the myosin heavy chain 1 (MYH1) gene found in certain muscle fibers of the horse.

Testing is available, but while research indicates that having a single copy of the MYH1 mutation makes a horse more susceptible to IMM or non-exertional rhabdomyolysis, not all horses with the mutation seem to contract the conditions. Therefore, the MYH1 genetic mutation is said to be dominant with incomplete penetrance, meaning one copy is enough to get the condition but not every horse with one or two copies will be affected.

Experts say there are some steps owners can take if they know their horse has one or two copies of the MYH1 mutation to try to lessen the chances of their horse developing either painful condition. And, because both of these conditions damage muscles quickly, knowing what to look for is key to getting a horse immediate treatment and stopping the damage as fast as possible.

The MYH1 Mutation

Michigan State University Large Animal Sciences Professor Dr. Stephanie Valberg, who in 2018, along with Dr. Carrie Finno at the University of California (UC) Davis and others, published “A missense mutation in MYH1 is associated with susceptibility to immune-mediated myositis in Quarter Horses,” said horses with IMM could lose more than one-third of their muscle mass across their topline in a matter of 48 hours. Those with non-exertional rhabdomyolysis, most often young horses, were sometimes in such pain they could not stand up and were euthanized.

Valberg refers to the two conditions as myosin heavy chain myopathy, as both are connected to the MYH1 genetic mutation. Research found that some Quarter Horses and related breeds are more likely to have the MYH1 mutation; it is specifically more prev-alent in reining, reined cow horse and halter bloodlines.

Horses with at least one copy of the MYH1 genetic mutation are at risk for immune mediated myositis (IMM), a condition where the body attacks its own muscle fibers. Horses suffering from IMM, such as this one, lose massive amounts of muscle along their croup and topline. • Photo courtesy of Dr. Stephanie Valberg.

Though research has not yet determined in which horse the mutation originated, Valberg said it is carried by enough horses that it is not a recent creation and appears likely to have begun around the time the Quarter Horse breed originated.

However, just because a horse has the MYH1 mutation doesn’t mean it will get IMM or suffer from severe non-exertional rhabdomyolysis. That happens, Valberg said, when the mutated gene in the muscle is exposed to the horse’s immune system. She said the trigger was often connected with strangles, or Streptococcus equi, because a protein in the strangles bacteria is similar to the horse’s mutated myosin gene.

“In these horses, it mistakes the myosin protein for strangles protein, and it attacks its own muscles,” she said.

In addition to strangles, IMM and non- exertional rhabdomyolysis can also be triggered by anything that causes inflammation in the muscle that would expose the fibers to the immune system, such as a vaccine reaction.

The MYH1 mutation is co-dominant, meaning having just one copy of the mutation — characterized in tests as N/My — is enough for a horse to be more susceptible to IMM or non-exertional rhabdomyolysis. Contrarily, having two copies of the mutation, which shows up on tests as My/ My, doesn’t guarantee a horse will get either condition, though Valberg has seen through anecdotal evidence that reactions tend to be worse among horses with two copies of the mutation than those with one copy.

“It’s common enough that if you have one copy of it, then you are susceptible to developing either of these two diseases, but if you have two copies, you are even more likely to develop it,” she explained. “And, if it does develop, the disease is more severe [for My/ My horses].”

While IMM and non-exertional rhabdomyolysis are separate disorders, Valberg said some horses that recover from non- exertional rhabdomyolysis later develop IMM. In addition, 40% of horses that developed IMM in the original research study experienced it again.

Living with IMM

Because the two conditions in myosin heavy chain myopathy are triggered by environmental factors, experts say testing can help horse owners manage their show or pleasure horses the best way possible. And, although Valberg knows of some show horses with one copy of the mutation and a few that have two copies, research doesn’t yet indicate how likely a horse with one or two copies is to develop either condition associated with the mutation.

Experts also don’t know how many Quarter or Paint horses have the mutation, because testing isn’t mandatory.

Experts don’t know how many Quarter or Paint horses have the mutation, because testing isn’t mandatory for registration; however, UC Davis found 0.3% — or roughly three in 1,000 — of the horses tested through the UC Davis Veterinary Genetics Laboratory were homozygous (My/My) for the genetic mutation.

Dr. Rebecca Bellone, director of the UC Davis Veterinary Genetics Laboratory, said approximately 13.7% had one copy of the mutation (N/My) and about 85% did not have any copies of the mutation (N/N).

“We recommend testing for Quarter Horses and Quarter Horse-related breeds,” Bellone said. “And, particularly in those subdisciplines where a higher frequency of the mutation has been reported.”

Knowing if a horse has the mutation allows owners to work with professionals to minimize the risk of a horse developing an immune response. Bellone and Valberg said it was imperative for owners to share their horses’ test information with their veterinarians.

“Strangles is one thing that we’ve seen very frequently can trigger either of those two diseases, and sometimes the vaccination for strangles will also trigger those two diseases if the horse has one or two copies of the genetic mutation,” Valberg said. “So, that’s one thing we do recommend people think about, [that] it’s probably not a good idea for those individuals to be vaccinated for strangles.”

Another management practice to follow is minimizing the damage to muscles because that could provoke an immune response. This can happen when a horse has a reaction to a vaccine other than strangles.

Vaccines, particularly for Strangles, have been reported as a potential trigger for IMM. Owners of horses with the MYH1 mutation are urged to work with their vet to create a vaccine program that reduces the chance of triggering muscle inflammation that can lead to an attack of IMM. • Photo by Kate Bradley Byars.

“If they have a vaccine reaction, like my horse who always blows up when you vaccinate him, there’s inflammation in the muscle. Then, the immune system also gets to see that [mutated MYH1] protein and reacts to it, starting an immune response against this protein in different muscles.”

Valberg suggested owners with horses that have one copy of the mutation work with their veterinarians to vaccinate using the least invasive method possible — whether that be through the horse’s nose or giving the fewest vaccines possible.

Before administering a vaccine to a horse with the MYH1 mutation, she said owners should alert their veterinarians that the animal is at risk for IMM or non-exertional rhabdomyolysis. They should also watch the horses closely after giving the vaccines and, if they see any signs of muscle pain or atrophy, immediately contact their veterinarian for treatment with corticosteroids.

“[IMM] starts right along the spine. The first signs you see is, all of a sudden, the spine starts to become more prominent, and then it starts to affect the top of the butt, so you don’t have a big rounded butt; it starts to hollow out a little bit,” Valberg explained. “And it will happen really, really fast. Literally, these horses will lose a third of the muscle on the top of their body within two to three days. It just melts away.”

In addition to using MYH1 testing as a management tool, Bellone said it also allows breeders to make informed decisions about mating horses with copies of the mutation. “Horses with one copy of the mutation are at an elevated risk, so you could utilize that information to make decisions on who to breed to [in order to] minimize the production of horses with the IMM allele,” Bellone said.

New Information

The future of MYH1-related research will seek to answer several questions, including how likely a horse with the mutation is to develop IMM or non-exertional rhabdomy- olysis. Currently, researchers don’t know that information.

Valberg said people who submit future genetic tests to UC Davis will be asked to answer an anonymous survey about their horse’s performance level and if it has had any symptoms of myosin heavy chain myopathy.

The answers to those questions — including whether or not the horse has ever shown clinical signs of the conditions — will pro- vide a clearer picture of how vulnerable horses with the mutation are to developing the conditions. It’s especially important owners of unaffected horses respond to such a survey, because people usually only reach out to Valberg and other researchers when their horses are sick, not when they are doing well.

“People are much more motivated to answer the survey if their horses have a disease, but if the Quarter Horse industry wants to know, ‘How likely is my horse to develop this?’ we need all the people whose horses are normal to answer that survey, too, so we have a representative population of horses and not a biased sampling of only ones that have the disease.”

This article appeared in the June 1, 2020, issue of Quarter Horse News.