The MDR1 Gene in Dogs
Overview of the Multi-Drug Resistance (MDR1) Gene in DogsThe multi-drug resistance (MDR1) gene commonly comes up as it is related to how some drugs affect dogs.You may have a new dog and followed your veterinarians recommend for spaying and neutering. But what about the MDR1 gene? Has your dog been tested? If not, you will definitely want to ask your veterinarian about it – especially if your dog is one of the affected herding or hound breeds, as it can cause life-threatening complications.In the grand scheme of things, the mutation wouldn’t be a problem at all except for the use of certain therapeutic drugs in veterinary practice. While these drugs are very beneficial for most dogs, they can be dangerous and even lethal to those with the MDR1 mutation.
How the (MDR1) Gene Works
In “normal” dogs – those that do not carry the mutation – the multi-drug resistance (MDR1) gene encodes P-glycoprotein (P-gp) – a large transmembrane protein that is an integral part of the blood-brain barrier. P-gp is responsible for pumping drugs and other toxins out of the brain and back into the bloodstream where they can be safely metabolized.
A mutation in MDR1, known as MDR1-1Δ, causes defects in the coding of P-gp, and, as a result, affected dogs do not produce the complete protein therefore hindering their ability to pump out certain substances. Drugs then accumulate inside cells where they can reach toxic, life-threatening levels.
Dog Breeds Affected with MDR1
Since Dr. Mealey’s discovery, researchers have identified more than 20 therapeutic drugs including loperamide (better known as Immodium, an over-the-counter anti-diarrhea agent) that are known substrates of P-glycoprotein and have been reported to cause problems in Collies, as well as nine related breeds known to carry the MDR1 mutation.
Those breeds being the Australian Shepherd, English Shepherd, German Shepherd Dog, McNab, Old English Sheepdog, Shetland Sheepdog, and two sight hounds—the Longhaired Whippet and Silken Windhound.
Interestingly, the allele that predisposes dogs to multi-drug sensitivity was not found in the Border Collie, Bearded Collie, or Australian Cattle Dog – three herding breeds that have reportedly exhibited ivermectin sensitivity.
Symptoms of MDR1 in Dogs
Symptoms of neurotoxicity may vary and can include:
- Lack of muscle coordination
- Excessive salivation
- Dilated pupils
- Respiratory distress
Diagnosis of MDR1 Gene Issues in Dogs
In 2001, Katrina Mealey, DVM, Ph.D., of the Washington State University College of Veterinary Medicine, identified the mutation in Collies. Since then, groundbreaking research has led to a host of scientific breakthroughs, including a simple cheek-swab test that can identify dogs as negative or positive for the mutation. The test is a bit costly at $70 but well worth the peace of mind it brings if your dog requires certain medications.
Three possible test results exist:
- Normal / Normal (n/n): These dogs do not carry the mutation, will not pass the mutation to their offspring, and would not be expected to experience unexpected adverse drug reactions.
- Mutant / Mutant (m/m): These dogs carry the mutation, will pass on the mutant gene to their offspring, and would be expected to experience toxicity after normal doses of certain drugs.
- Mutant / Normal (m/n): These dogs carry the mutation, may pass on the mutant gene to their offspring, and may experience toxicity after normal doses of certain drugs.
Treatment of MDR1-1Δ Positive Dogs
What are the implications for your dog tests positive for the MDR1Δ
The short-term implications are that herding breed dogs (and mixed breeds) should not receive some drugs until they are tested (and are negative) for the mutation.
The most important drugs to be concerned about are ivermectin, the chemotherapeutic agents vincristine and doxorubicin, acepromazine (tranquilizer), and butorphanol (pain control). Ivermectin dosage used in commercial preparations such as Heartguard, Revolution, Interceptor, etc., are safe for dogs with the mutation, according to Mealey.
Interestingly, affected dogs can experience toxicity if they eat livestock feces from animals that have been treated with larger doses of ivermectin. Researchers say not all of the ivermectin is metabolized in the livestock. Those yummy “road apples” consumed by dogs carrying the mutation can cause neurotoxicity.
As research continues, it is highly likely that more pharmaceuticals will continue to be added to the existing list of problem drugs. However, a simple test will keep affected dogs safe and healthy for years to come.