When a horse is tested for PSSM2 they can come back Heterozygous (n/p8) or Homozygous (P8/P8) but what exactly is P8?

What Is P8?

P8 is a variant of MFM (Myofibrillar myopathy) that is available to test for under the PSSM2 test.

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 cause muscle weakness, and loss of muscle mass.

What Does The P8 Variant Affect?

The P8 variant affects something called Pyridine nucleotide-disulphide oxidoreductase domain 1.

What Is Pyridine Nucleotide-Disulphide Oxidoreductase Domain 1?

Pyridine nucleotide-disulphide oxidoreductase domain 1 is a flavoprotein that’s encoded as the PYROXD1 gene.

What Is The Function Of Pyridine Nucleotide-Disulphide Oxidoreductase Domain 1?

Pyridine Nucleotide-Disulphide Oxidoreductase Domain 1 plays a vital role in DNA repair, photosynthesis in plants, and removal of radicals a process also better known as Oxidative defence. Radicals are oxygen-containing molecules with an uneven number of electrons. This imbalance in electrons allows Radicals to easily react with other molecules causing large chain chemical reactions called oxidative stress which causes toxic effects in the body through the production of peroxides and further free radicals.

What Happens When There Is A Gene Mutation In Pyridine Nucleotide-Disulphide Oxidoreductase Domain 1?

When a genetic mutation occurs in Pyridine Nucleotide-Disulphide Oxidoreductase Domain 1, the mutated PYROXD1 will fail in its function to maintain the correct redox state of cysteine thiols in a large number of target proteins, the normal redox state in cells is the state at which atoms are changed within the body, the change to this normal redox state causes protein misfolding and clumps also known as aggregates. Because Pyridine Nucleotide-Disulphide Oxidoreductase Domain 1 also plays a role in Cysteine Oxidative defence, this means the horse’s ability to remove free radicals from the body related to Cysteine will be compromised. If a horse has more free radicals in the body than can be kept in balance by antioxidants then damage can occur to fatty tissue, DNA, and proteins in the body.

How Does Having A Mutation In Pyridine Nucleotide-Disulphide Oxidoreductase Domain 1 Cause A Horse To Be Symptomatic?

Let’s look at this in an easy way- having mutations in Pyridine Nucleotide-Disulphide Oxidoreductase Domain 1 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 P8 At Different Ages?

Because every horse’s body is different. Some horse’s bodies are stronger, some horse’s 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 can’t 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!

For more information on the P8 variant of PSSM2 check out our YouTube video by clicking this link