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The MDR1 Gene in Dogs

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:

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:

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.