The vast majority of genes in the body are important and indispensable for life.
And most of them are not known by the general population. Many are even unknown to the geneticists themselves, hidden within the genome, among the multitude.
However, the MDR1 gene (multidrug resistance protein 1) is not one of them. It is so well-known that there are multiple genetic tests at different prices for the MDR1 gene.
The MDR1 Gene and Its Importance in Your Pet
Also known as the ABCB1 gene (ATP-binding cassette sub-family B member 1), it encodes a protein called P-glycoprotein, permeability glycoprotein, or Gp-P. Choose whichever name you prefer.
This glycoprotein is located in the cell membrane and serves to expel substances out of the cell.
Up until now, nothing extraordinary. Other proteins do the same.
But few have such a broad capacity to interact with other molecules like MDR1. It is a highly conserved gene across many organisms, due to its protective function against harmful substances.
There is an unwritten rule in biology that suggests when something is conserved throughout evolution, it must be very valuable. You won’t find the same characteristic in species separated by millions of years if it weren’t crucial for survival.
Furthermore, it is found in the blood-brain barrier, controlling which molecules can cross it. This barrier separates (and isolates) the brain from the rest of the body.
This transporter is one of the key factors in deciding what can enter the brain, and what stays inside.
Although far from being exclusive to the brain, as its distribution throughout the body is extensive: digestive, liver, kidney systems, etc.
As mentioned earlier, we can understand the importance of the MDR1 gene in the animal’s response to pharmacological treatments. And any mutation altering its function also alters the pharmacological response, which carries risks.
What Happens When the MDR1 Gene in Dogs is Defective?
Most mutations in this gene are considered autosomal dominant with incomplete penetrance.
The gene is autosomal because it is located on chromosome 14 in dogs, not a sex chromosome. Therefore, the risk of disease is independent of the animal’s sex.
Incomplete penetrance means that the same mutation can result in different phenotypes depending on the animal. In other words, having the mutated gene does not guarantee that the animal will always develop the disease. The disease does not have the same intensity in all affected animals.
Additionally, the severity of the pathology is correlated to the number of affected gene copies. An animal with both copies of the MDR1 gene mutated will suffer more severe effects from medications than dogs with just one affected copy.
With the Koko Genetics Dog DNA Test, you will see three possible results for your pet:
- No trait present: Congratulations! Your dog is healthy, at least in regards to the MDR1 gene. You don’t need to worry about anything; the animal should not express this trait.
- One copy present: One copy of the MDR1 gene is defective and the other is normal. As this is an incompletely penetrant gene, we cannot predict the intensity of the pathology without more information. Inform your vet and remember that your dog’s offspring may inherit the defective copy as well.
- Two copies present: Both copies of your dog’s MDR1 gene are defective. Sadly, this is the worst-case scenario. Your pet will suffer the pathology more severely than if only one copy were affected. Contact your vet as soon as possible and consult a professional before administering any treatment and/or pharmaceutical operation to your dog. Its offspring will always inherit at least one defective copy of the gene.
It is extremely rare for the mutation to occur de novo. Unless in exceptional cases, the presence of the mutated gene in an animal indicates that one or both of its parents had at least one defective copy, which they passed on to their offspring.
That’s why it’s so important to conduct genetic testing on animals from breeds predisposed to these mutations or when suspected. This helps avoid further inheritance of the defective gene.
Breeds Affected by the MDR1 Gene
Not all breeds have the same probability of developing this condition. Since it is hereditary, those breeds in which affected animals have been used in breeding programs tend to have more frequent related pathologies.
The breed most commonly associated with the disease is the Border Collie. However, it is far from the most affected. The most affected breeds are the Long-Haired Collie and Short-Haired Collie. It is estimated that approximately three out of every four Collies have at least one defective copy of the MDR1 gene.
However, although Collies are the most frequently affected, they are not the only ones. The gene can be found in other shepherd dogs and greyhounds, such as the Australian Shepherd, Mini Australian Shepherd, McNab, Silken Windhound, German Shepherd, Whippet, Huntaway, Old English Sheepdog, Shetland Sheepdog, and the Swiss White Shepherd.
If your dog belongs to one of the breeds with a higher likelihood of having a defective MDR1 gene, we recommend testing it.
When the protein encoded by the MDR1 gene does not work properly, an abnormal accumulation of substances occurs in the central nervous system.
Many drugs that would normally be filtered and eliminated by the Gp-P protein now pass through the blood-brain barrier more easily and stay there.
Therefore, medication doses that cause expected effects in a healthy dog can result in toxically high concentrations in the brain of a dog with the defective MDR1 gene.
Symptoms and Prohibited Medications for the MDR1 Gene
Depending on the situation, the results can range from seizures and neurological attacks to coma or even death. The main symptoms are:
– Vomiting.
– General weakness.
– Uncoordinated movements.
– Tremors and shakes.
– Blindness.
– Coma and/or death (in extreme cases).
Not all drugs interact with this gene, nor do all cause problems when the gene is defective.
Some of the medications prohibited by the MDR1 gene include:
– Ivermectin: Used to treat parasitic infections, from ticks to heartworms.
– Analgesics and sedatives: Such as butorphanol and acepromazine.
– Loperamide: A commonly used anti-diarrheal drug, but in dogs with defective MDR1, its passage into the brain causes significant damage.
An additional problem with abnormal gene variants is the need to modify pharmaceutical treatments.
Some drugs may not meet their intended goals, as the doses must be lowered to avoid harm to the animal. When this happens, if there are no other alternatives, we are forced to choose the lesser of two evils.
Another issue is the synergy between medications. Not only must we consider the relationship between a drug and the defective Gp-P transporter, but also the interactions with other drugs.
Common treatments include reducing doses whenever possible and/or using other alternatives.
As with most genetic diseases, conditions arising from a rare MDR1 gene mutation are chronic. There is no cure, and the animal must live with its condition.
To avoid unpleasant surprises, we recommend testing for the MDR1 gene. And if the cost of these genetic tests concerns you, we recommend the Koko Genetics Pet DNA Test, which economically includes this gene among many others.