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 a variant of RER (Recurrent Exertional Rhabdomyolosis)
What is Recurrent Exertional Rhabdomyolosis?
Recurrent Exertional Rhabdomyolosis 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 for example, it also assists in the assembly of the voltage gated calcium channel.
Unfolding and folding of a protein molecule
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 horses 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 heart beat, and fluid balance.
Calcium Ion
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 allelle, the mutated PX allelle is like that annoying fly who keeps buzzing round your head, it's not wanted and it causes havoc! The mutated PX allele splices which means it deletes, changes, and alters the sequence of CACNA2D3 single stranded molecules called primary transcript inserts. These single stranded molecules are essential for, decoding, regulation and expression of genes.
How does having a mutation in CACNA2D3 cause a horse to be symptomatic?
Lets look at this an easy way- having a mutation in CACNA2D3 caused by the PX allele is like a book with missing pages, back to front words, and lots of crossings out!
The book still tells a story, but you won't be able to understand or make sense of much of it as parts have been ripped out and changed and this is what happens in PX horses, as the PX allele changes and deletes information in CACNA2D3 it makes it difficult for the CACNA2D3 single stranded molecules to code, decode, regulate and express genes, making their use prohibited and their story a mess of confusion.
Why are horses affected by PX 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!
Where can I find more information on PX?
Be sure to head over to Equiseq to check out their blog on RER (PX) below
Our Study On PX Horses?
In a large survey we are still conducting of all PSSM variants we have 200 surveys. Of these 200, 21 of those horses where either Heterozygous or Homozygous for the PX variant and here is what we found:
Breeds affected by the PX variant in our survey were all American Quarter Horses, American Paint Horses, Appaloosas, Connemaras, Irish Draughts, Thoroughbreds and Warmbloods.
Affected horses ranged from 1 month old-10 years old, the most common ages for PX to strike were 4, 5 and 10 years old.
12 horses were Heterozygous for PX (n/Px) while 9 horses were Homozygous for PX (PX/PX)
The most common symptoms of PX were Explosive behaviour, and Canter issues with with 11 out of 21 horses displaying these 2 symptoms while 5 horses were foals being the only unsymptomatic horses on our PX survey.
Other symptoms displayed by horses included:
Aggression/ Camping out (standing out to pee but not going)/ Bunny hopping/ Colic or Laminitus like symptoms/ Contact Issues/ Dark or bloody urine/ Depression/ Exercise intolerance/ Lameness/ Lethargy or laziness/ Losing topline/ Muscle spasms/ Reluctance to be saddled/ Sensitivity/ Standing under themselves/ Stiffness/ Tight Muscles/ Sweating Profusely and breathing heavily/ Tying up or Azoturia
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