The P3 Variant Of PSSM2 Explained

When a horse is tested for PSSM2 they can come back heterozygous (N/P3) or homozygous (P3/P3) but what exactly is P3?

What Is P3?

P3 is a variant of MFM (Myofibrillar myopathy)

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 P3 Variant Affect?

The P3 variant affects something called Filamin-C

The P3 Variant Of PSSM2 Explained

What Is Filamin-C?

Filamin-C is an actin binding protein that’s encoded as the FLNC gene, it is made up of 2,725 amino acids and is one of the largest proteins found in cardiac and skeletal muscle. Filamin-C gives the whole muscle structure strength along with other actin binding proteins- think of it a bit like glue it helps hold everything together.

What Is Filamin-C?
Equine Skeletal Muscle- Filamin-C works together with other actin binding proteins in holding all those muscle fibres together

What Is The Function Of Filamin-C?

We know the family of Filamin proteins participate in anchoring membrane proteins for the Actin Cytoskeleton; the Cytoskeleton is a structure that helps muscle cells maintain their shape both inside and out, the Cytoskeleton also provides mechanical support to cells to enable them to carry out actions like movement. However the exact function of Filamin-C is still under investigation but as Filamin-C is found in the cell membranes of muscle cells, and in Z disks, Filamin-C is thought to act as a mode of communication between the muscle membrane and the muscle itself- think of it a bit like a telephone line!

What Happens When There Is A Gene Mutation In Filamin-C?

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

How Does Having A Mutation In Filamin-C Cause A Horse To Be Symptomatic?

Lets look at this in an easy way- We believe Filamin C acts as a mode of communication. If there is a break in that line of communication it means messages cannot get through to muscle cells, it’s like trying to have a telephone conversation with a crackly line you might receive some words but its really hard to hear, but as time goes on that connection will become weaker, and weaker, until eventually you won’t be able to hear anything at all! This is what happens in PSSM2 horses, the mutation in that one gene affects the rest of the muscle structure as Myotilin, Myozenin, and Filamin C all work together, 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 P3 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 P3 Horses

In a large survey we are still conducting of all PSSM variants we have 200 surveys. Of these 200, 20 of those horses where either Heterozygous or Homozygous for the P3 variant and here is what we found:

  • Breeds affected by the P3 variant in our survey were all American Quarter Horses, American Paint Horses, Appendix Quarter Horses, Belgians, Cobs, Connemara’s, Irish Draughts, German Riding Ponies, Rocky Mountain Horses, a range of Warmbloods and Welshes.
  • Affected horses ranged from 1-16 years old, the most common ages for P3 to strike were 4 and 7 years old.
  • 18 horses were Heterozygous for P3 (n/p3) while 2 horses were Homozygous for P3 (P3/P3)
  • The most common symptoms of P3 were Lethargy, Lameness, Stiffness, Tight Muscles, and Struggling with Canter with 15 out of 20 horses displaying these 5 symptoms.

    Other symptoms displayed by horses included:
    Sensitivity/ Aggression/ Camping Out/ Contact Issues/ Dark/Bloody Urine/ Depression/ Losing Topline/ Standing Under Themselves/ Breathing Heavily and Sweating Profusely/ Muscle Spasms/ Tying up or Azoturia/ Colic or Laminitus like symptoms/ Explosive Behaviour/ Reluctance to be Saddled/ Respiratory Problems/ Trouble standing for Farrier/ Trouble to stand in the horsebox or trailer/ Balance Issues/ Stumbling/ Exercise intolerance/ Ulcers

For more information on the P3 variant of PSSM2 check out our YouTube video by clicking this link