The P2 Variant Of PSSM2 Explained

When a horse is tested for PSSM2 they can come back Heterozygous (N/P2) or Homozygous (P2/P2) but what exactly is P2?

What Is P2?

P2 is a likely variant of MFM (Myofibrillar myopathy). It is only known as likely because there is no evidence of mutations in the gene that’s affected in P2 being associated with MFM in horses, however there is evidence of this in humans.

What is Myofibrillar Myopathy?

Myofibrillar Myopathy or MFM is part of a group of disorders known as muscular dystrophy. Muscular dystrophy is a progressive disease caused by abnormal/mutative genes that causes muscle weakness, and loss of muscle mass.

What Does The P2 Variant Affect?

The P2 variant affects something called Myotilin

The P2 Variant Of PSSM2 Explained

What Is Myotilin?

Myotilin is a structural protein that’s encoded as the MYOT gene. Think of it a bit like cement it helps hold everything together. Myotilin gives structural strength and stability to sarcomeres in z disks which are units of streaky muscle tissue.

What Is The Function Of Myotilin?

Myotilin encourages formation of something called actin bundles (multi functional proteins) in vitro and non muscle cells. Myotilin stabilises something called F-actin (protein) by slowing down the rate at which F-actin (protein) is broken down.

What Happens When There Is A Gene Mutation In Myotilin?

When a genetic mutation occurs in Myotilin the mutated Myotilin clusters together causing clumps also known as aggregates, these clumps prevent the proteins in muscles functioning normally.

How Does Having A Mutation In Myotilin Cause A Horse To Be Symptomatic?

Lets look at this in an easy way- having mutations in Myotilin is like building a house with no cement; you can still build it but at some point in time the house will crumple and fall to the ground. This is what happens in PSSM2 horses, the mutation in that one gene affects the rest of the muscle structure, it might work for a little while but it is weakened, and as PSSM2 is degenerative as time goes on more clumps occur and the muscle structure will become weaker, and weaker, leading a horse to eventually become symptomatic.

Why Are Horses Affected By P2 At Different Ages?

Because every horses body is different. Some horses bodies are stronger, some horses bodies are weaker, some horses are immature, while others are more mature, some horses are able to withstand pain and even grow accustomed to it, and some horses simply cant take the slightest ounce of pain and will let you know that something is wrong- Every single horse is an individual and different just like us!

Our Case Study On P2 Horses

In a large survey we are still conducting of all PSSM variants we have 200 surveys. Of these 200, 32 of those horses where either Heterozygous or Homozygous for the P2 variant and here is what we found:

  • Breeds affected by the P2 variant in our survey were all American Paint Horses, American Quarter Horses, Arabians, Appaloosas, Belgians, Hackneys, Thoroughbreds, and Warmbloods.
  • Affected horses ranged from 1-18 years old, the most common ages for P2 to strike were 3, 4, 5 and 6 years old.
  • 27 horses were Heterozygous for P2 (n/p2) while 5 horses were Homozygous for P2 (P2/P2)
  • The most common symptoms of P2 were Stiffness, Tight muscles, Explosive Behaviour, and Lameness with 21 out of 32 horses displaying these 4 symptoms.

Other symptoms displayed by horses included:
Canter issues/ Reluctance to be saddled/ Lethargy/ Sensitivity/ Not forwards under saddle/ Sweating profusely and breathing heavily after small amounts of work/ Standing under themselves/ Aggression/ Camping out/ Contact issues/ Dark or bloody urine/ Losing topline/ Muscle spasms/ Colic or laminitis symptoms/ Falling over/ Muscle divots/ Depression/ Tying up/ Exercise intolerance/ Farrier troubles/ Resting back legs/ Biting at sides/ Back end weakness/ Tripping.

For more information on the P2 variant of PSSM2 check out our YouTube video by clicking this link