Individual predisposition
Genetic variants can influence the structural and functional prerequisites of the musculature. Individual factors may act strongly, others only in combination.
Exertional myopathies in horses
Muscle problems in horses don't always have just one cause.
PSSM1, PSSM2, MIM and RER describe different relationships. Modern genetic diagnostics help to make an important part of a horse's individual biological predispositions visible.
Exertional myopathy: a symptom complex with different causes
Muscle stiffness, pain, reluctance to move, drops in performance, difficulty building muscle or recurring episodes of “tying-up” can be signs of an exertional myopathy. However, the term does not describe a single disease, but a spectrum of different disorders of the musculature.
Training, feeding, stress
Exercise, recovery, energy and protein supply and further environmental factors also help decide whether a genetic predisposition becomes clinically apparent.
Similar symptoms, different causes
The fact that two horses show similar muscle problems does not necessarily mean that the same biological cause underlies them.
PSSM1, PSSM2, MIM and RER: not the same thing
PSSM1
A genetically defined polysaccharide storage myopathy. A variant in the GYS1 gene alters glycogen metabolism. Here there is a clear molecular link.
PSSM2
A histopathologically described polysaccharide storage disorder in horses without the GYS1 variant responsible for PSSM1. The genetic causes are so far not clearly established.
MIM
A concept of genetically co-influenced disorders or reduced resilience of the structure and function of the muscle cell. MIM is not to be equated with PSSM2.
RER
Recurrent Exertional Rhabdomyolysis describes recurring exercise-related episodes of muscle breakdown. Here, too, genetic and non-genetic factors can interact.
MIM – Muscle Integrity Myopathy
The variants previously offered under the name “PSSM2 test” are today grouped at Generatio under MIM. The reason: they do not detect a polysaccharide storage disorder, but lie in genes whose products are involved in different structural or functional processes of the muscle cell.
P2 · MYOT
Myotilin; a component of the Z-disc and involved in organising the muscle fibre structure.
P3 · FLNC
Filamin C; an important structural protein of striated muscle.
P4 · MYOZ3
Myozenin 3; a Z-disc protein with structural and regulatory functions.
Px · CACNA2D3
A subunit of voltage-dependent calcium channels; relevant to cellular signalling processes.
P8 · PYROXD1
A protein of importance for cellular redox processes and muscle function.
K1 · COL6A3
A component of collagen VI and thus of the extracellular matrix of the musculature.
What does the MIM 6-variant test tell you?
The test does not answer the question “Is my horse sick?”. It answers the question: Which of the examined genetic variants does my horse carry?
Genetic information
Whether P2, P3, P4, P8, Px or K1 are present and whether the respective variant is detected as heterozygous or homozygous.
No stand-alone diagnosis
A positive result does not automatically mean that a horse is or will become ill. A negative result does not rule out other genetic or non-genetic causes of muscle problems.
Why genetic factors matter in complex diseases
Complex does not mean insignificant. Even if a single genetic factor does not cause a disease on its own, knowing the genetic starting point can help to better assess an individual horse's situation.
Genetics
Training
Feeding
Recovery & environment
Individual phenotype
What do the studies show – and what do they not show?
In widely cited investigations by Valberg and colleagues, it was examined whether P2, P3 and P4 in particular match, or can predict, the histopathological diagnoses of PSSM2 or MFM used at the time. Such a diagnostic association could not be shown in the populations studied.
For multifactorial diseases, different requirements therefore apply than for a highly penetrant monogenic defect. Relevant factors include effect size, penetrance, interactions with other genes and environmental factors, as well as the link to clearly defined functional or clinical endpoints.
Note: This page deliberately distinguishes between confirmed variant detection, biological plausibility, functional evidence and clinical interpretation. Statements about individual variants should be updated regularly as the body of studies progresses.
How to mate with MIM in mind?
With genetic risk factors of a complex, multifactorial disease, the goal is not to exclude every animal carrying a variant from breeding across the board. It makes more sense to use targeted mating planning that takes the genetic starting point of both parent animals into account.
Do not combine the same variant with each other
If both breeding partners carry the same MIM variant, offspring can arise that inherit this variant from both parents. In mating planning, it should therefore be a priority to avoid the same risk variant coming together from sire and dam.
Limit the accumulation of several variants
Beyond the single genotype, the entire variant profile of both parent animals should be considered. Where several risk variants may come together, a cautious mating plan that avoids unnecessary accumulation is sensible — as long as variant-specific effect sizes and possible interactions are not conclusively clarified.
Do not exclude variant carriers across the board
A heterozygous finding alone should not automatically lead to exclusion from breeding in a multifactorial condition. By choosing a genetically suitable partner, the risk in the next generation can be reduced while valuable traits and genetic diversity are preserved.
Example: same variant
n/P2 × n/P2: This mating should be avoided where possible under the precautionary principle, because P2/P2 offspring can arise.
The example describes the genetic inheritance of the variant. It is not a prediction of whether, or to what extent, an individual horse will develop clinical symptoms.
Example: take the variant profile into account
If a breeding animal already carries several of the examined variants, a partner should preferably be chosen whose MIM profile introduces as few additional risk variants as possible into the offspring.
This does not imply that the effects of the variants are simply additive. The strategy serves to limit avoidable genetic risk combinations while knowledge of the individual effect sizes is still incomplete.
Know more for a responsible breeding decision
For recurring muscle problems, noticeable exercise intolerance, or if you would like to better understand your horse's genetic predispositions, the MIM 6-variant test can provide an additional building block of information.
You receive clear genetic information on six defined variants. This can help to place observations on the horse more precisely, to sharpen questions for further veterinary investigation and to make management decisions more consciously.
The test does not replace a veterinary examination or a clinical diagnosis. Breeding, purchase or treatment decisions should not be based on a MIM finding alone.