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

What is PX?

PX is not a variant of PSSM2, but it is a suspected variant of RER (Recurrent Exertional Rhabdomyolysis)

What is Recurrent Exertional Rhabdomyolysis?

Recurrent Exertional Rhabdomyolysis or RER is a form of exercise intolerance caused by an abnormality of calcium regulation in muscle cells.

What does the PX variant affect?

The PX variant affects something called the CACNA2D3 gene

What is the CACNA2D3 Gene?

The CACNA2D3 gene is a protein that assists in the folding and unfolding of large molecular structures like protein, it also assists in the assembly of the voltage-gated calcium channel.

What is the function of CACNA2D3?

CACNA2D3 encodes a member of the alpha-2/delta subunit family, a protein in the CA2+ Ion channel complex. CA2+ Ion channels are selective tunnel-like structures that change shape to allow charged Calcium Ions through. Calcium Ions contribute to the way in which bodily parts function and biochemical processes within muscle cells. Some of the many functions Calcium Ions contribute to in a horse’s body are muscle contraction, blood clotting, bone and teeth strength, nerve impulses, oocyte production (starting egg production in mares), transmission (electrical impulses in the body), regulating heartbeat, and fluid balance.

What happens when there is a genetic mutation in CACNA2D3?

When a genetic mutation occurs in CACNA2D3, the quantity of CACNA2D3 and the channel density in the membrane is altered by the interference of the mutated PX allele, the mutated PX allele is like that annoying fly who keeps buzzing around your head, it’s not wanted and it causes havoc! The mutated Px allele likely changes the way that the mRNA copy of the gene is processed. mRNA is the information that is used to synthesize the CACNA2D3 protein, so changes in the processing of mRNA affect the level of expression of the protein.

How does having a mutation in CACNA2D3 cause a horse to be symptomatic?

Having a mutation in the CACNA2D3 gene alone doesn’t cause a horse to be symptomatic. The PX variant of PSSM2 only causes a horse to develop symptoms if they are diagnosed with another variant of PSSM2 for example N/PX & N/P2, or if they have an undiscovered variant of PSSM2 alongside the PX- this is why some N/PX horses are highly symptomatic.

PX alongside any other variant of PSSM2 acts as an enhancer and can make symptoms much more pronounced.

What About Horses With PSSM1 & PX?

In horses, with PSSM1 and PX the same applies. PSSM1 does not interact with the PX variant of PSSM2 and cause issues if you have a horse who is:

-N/P1 & N/PX
-N/P1 & PX/PX
-P1/P1 & N/PX
-P1/P1 & PX/PX

Who is highly symptomatic with further symptoms than just PSSM1, it will be an undiscovered variant at play interacting with the PX that is causing the issues in your hybrid horse.

Why are horses affected by PX 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 PX variant of PSSM2 check out our YouTube video by clicking this link