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Clinical Overview

Multi-drug Resistance 1 (MDR1) is a genetic mutation found in many of the herding breeds, some sighthound breeds, and many mixed breed dogs. The MDR1 gene is responsible for production of a protein called P-glycoprotein. The P-glycoprotein molecule is a drug transport pump that plays an important role in limiting drug absorption and distribution (particularly to the brain) and enhancing the excretion/elimination of many drugs used in dogs.

Some dogs, particularly herding breeds or mixed-breed dogs with herding breed ancestry, have a mutation in the MDR1 gene that makes them defective in their ability to limit the absorption and distribution of many drugs. These dogs are also slower to eliminate drugs from the body that are transported by P-glycoprotein. As a result, dogs with the MDR1-mutation may have severe adverse reactions to some common drugs, so it is important to test your dog and share your results with your veterinarian so they can provide your dog with for the best possible care.

Drugs Affected by the MDR1 Mutation:

  • Acepromazine
  • Butorphanol
  • Doxorubicin
  • Doramectin
  • Doramectin
  • Emodepside
  • Erythromycin
  • Ivermectin
  • Loperamide
  • Milbemycin
  • Moxidectin
  • Paclitaxel
  • Rifampin
  • Selamectin
  • Vinblastine
  • Vincristine

Breeds Affected by the MDR1 Mutation (frequency %):

  • Australian Shepherd 50%
  • Australian Shepherd, Mini 50%
  • Border Collie < 5%
  • Collie 70%
  • English Shepherd 15%
  • German Shepherd 10%
  • Herding Breed Cross 10%
  • Long-haired Whippet 65%
  • McNab 30%
  • Mixed Breed 5%
  • Old English Sheepdog 5%
  • Shetland Sheepdog 15%
  • Silken Windhound 30%

FAQs About the MDR1 Mutation

Can Collie crosses or other herding breed crosses carry the mutant MDR1 gene and have an adverse reaction to a normal dose of some drugs?

Yes, it is less likely in a mixed breed, but still possible. For example, the mutant gene was found in a Saint Bernard mix that had an adverse drug reaction. The veterinarian did note that each eye was a different colour, like some Australian Shepherds.

How old must a dog be before it can be tested?

Just like breed testing, a puppy can be tested as soon as it is weaned from its mother. We recommend waiting until the puppy is weaned, because the sample is collected from inside the dog's mouth, and milk can contain a cells from the mother. Therefore, it is possible that the puppy's sample could contain enough of the mother's DNA to generate a false result.

Can mixed-breed dogs have the MDR1 mutation?

YES! Even if we don't find a pedigree herding or sighthound breed in the last three generations of your dog's family tree, doesn't mean he or she doesn't have one further back in their ancestry. Therefore, even mixed-breed dogs should be tested for the MDR1 mutation¬¬-in particular before receiving therapies for some common parasitic diseases, such as Demodectic mange. The results of this test can give owners with mixed-breed ancestry important information to share with their veterinarian or better yet…peace of mind. 

What heartworm prevention products can I use if my dog has the MDR1 mutation?

Always consult with your veterinarian before administering any drugs to your dog. Fortunately, the doses of ivermectin, selamectin, milbemycin and moxidectin in the FDA approved heartworm prevention preparations are low enough to be used safely even in dogs that have two copies of the MDR1 mutation. It is only when these drugs are administered at high doses that dogs with the mutation will develop signs of toxicity. Attempting to use formulations of these drugs approved for use in large animals will increase the risk of overdosing the dog and causing severe toxicity, because it is difficult to accurately measure the small doses needed for dogs using these large animal formulations.

Origins of the Test

The discovery of the mutation of the multi-drug resistant gene (MDR1) and its effects on multidrug sensitivity in dogs was made by Washington State University. It is a patent-protected diagnostic test offered by Washington State University that has been licensed to Wisdom Health for use in the WISDOM PANEL tests.