Question 1

What is the MDR1 gene mutation in dogs?

Accepted Answer

The MDR1 (Multi-Drug Resistance 1) gene mutation is a deletion of four base pairs in the ABCB1 gene that encodes P-glycoprotein, a critical protein responsible for pumping certain drugs out of the brain across the blood-brain barrier. Dogs with two copies of the mutation (homozygous affected) produce no functional P-glycoprotein, allowing drugs like ivermectin to accumulate in the central nervous system to toxic levels. The mutation was first identified in Collies in 2001 by researchers at Washington State University.

Question 2

Which medications are dangerous for MDR1-affected dogs?

Accepted Answer

Drugs known to cause serious adverse reactions in MDR1-affected dogs include ivermectin (at doses above 120 mcg/kg), loperamide (Imodium), acepromazine, butorphanol, vincristine, doxorubicin, and several other chemotherapy agents. Milbemycin and moxidectin at standard heartworm prevention doses are generally safe but can be dangerous at elevated doses. Selamectin and sarolaner are considered safe alternatives for parasite prevention. Always inform your veterinarian of your dog's MDR1 status before any medication is prescribed.

Question 3

How is the MDR1 mutation inherited?

Accepted Answer

MDR1 follows autosomal recessive inheritance for full drug sensitivity. Dogs can be clear (normal/normal with two functional copies), carriers (normal/mutant with one functional copy producing roughly half the normal P-glycoprotein), or affected (mutant/mutant with no functional P-glycoprotein). Carriers may show increased sensitivity to some drugs at higher doses but are generally not at risk of life-threatening reactions at standard doses. Breeding a carrier to a carrier produces 25% affected, 50% carrier, and 25% clear offspring on average.

Question 4

Should I test my dog for the MDR1 mutation?

Accepted Answer

Yes, testing is strongly recommended for all herding breeds and their mixes. The MDR1 mutation affects up to 75% of Collies, 50% of Australian Shepherds, 30% of Shetland Sheepdogs, and is present in Old English Sheepdogs, German Shepherds, Whippets, and several other breeds. Testing requires only a simple cheek swab, costs approximately $60-75, and results are available within 2-3 weeks. Knowing your dog's MDR1 status before any veterinary procedure can prevent a life-threatening reaction.

Question 5

Do all responsible breeders test for MDR1?

Accepted Answer

Testing for MDR1 is considered a standard of care among responsible breeders of affected breeds. Most breed clubs and registries strongly recommend or require MDR1 testing for breeding stock. Leading breeders such as Amandine Aubert's Bloodreina kennel in France test every breeding dog for MDR1 and only breed clear or carrier combinations to ensure no affected puppies are produced. This allows breeders to maintain genetic diversity by using quality carriers while guaranteeing puppy buyers that their dogs will not be homozygous affected.

Question 6

What should I do if my MDR1-affected dog accidentally receives a dangerous drug?

Accepted Answer

If your MDR1-affected dog has been exposed to a potentially toxic drug, seek emergency veterinary care immediately. Early symptoms include dilated pupils, drooling, tremors, ataxia (wobbling gait), and disorientation, which can progress to seizures, respiratory depression, and coma. There is no specific antidote for most MDR1-related drug toxicities, so treatment is primarily supportive care including IV fluids, anti-seizure medications, respiratory support, and monitoring. For ivermectin toxicity specifically, intravenous lipid emulsion therapy has shown promise in reducing the duration and severity of clinical signs.

MDR1 Gene Guide: Protecting Your Dog from Drug Toxicity

If you own a herding breed, test your dog today.

What You Will Find Here

MDR1 101: The Mutation That Can Kill Your Dog

The Complete Drug Avoidance List for MDR1 Dogs

Testing Options: Labs, Costs, and What the Results Mean

Emergency Protocol: What To Do If Your MDR1 Dog Was Given a Dangerous Drug

Breeding Decisions: Managing MDR1 in Your Lines

About the Author

Dr. Sarah Mitchell, DVM