MDR1 Gene Mutation in Dogs: Which Breeds Are Affected and What Drugs to Avoid

A dog that tests MDR1 affected or carrier can have a life-threatening reaction to medications considered safe for most dogs

The MDR1 mutation is a genetic variant that can turn routine veterinary medications into potentially fatal treatments. A dog with this mutation may react severely to drugs that are entirely safe in unaffected dogs. Understanding which dogs are at risk, which drugs are dangerous, and how to manage this mutation is essential knowledge for breeders and owners of herding breeds and their mixes.

What Is MDR1?

MDR1 stands for Multi-Drug Resistance 1, also called the ABCB1 gene. The protein this gene produces, P-glycoprotein, is a transporter that pumps certain drugs back out of the brain and other sensitive tissues. It acts as a protective barrier.

Dogs with the MDR1 mutation have defective or absent P-glycoprotein. Without this protective pump, certain drugs that should not cross into the brain can accumulate to toxic levels, causing neurological symptoms that range from disorientation and tremors to seizures, coma, and death.

Which Breeds Carry MDR1?

The mutation originated in a common ancestor of herding breeds. Breeds with the highest prevalence include:

Collies — The mutation was first identified here; prevalence exceeds 70% in some Rough Collie populations
Australian Shepherds — Approximately 50% carry at least one copy
Shetland Sheepdogs (Shelties)
Border Collies — Lower prevalence than Aussies and Collies but still significant
English Shepherds
German Shepherds — Lower prevalence (~10%) but a large population
McNab Shepherds
Old English Sheepdogs
Silken Windhounds
Longhaired Whippets

The mutation has also appeared in mixed-breed dogs with herding ancestry. Any dog suspected of herding breed ancestry should be tested.

Drugs That Are Dangerous in MDR1 Affected Dogs

The following drugs have caused serious adverse reactions in MDR1 mutant dogs. This is not an exhaustive list — any drug that is a substrate of P-glycoprotein carries risk:

Antiparasitic drugs:

Ivermectin (heartworm prevention at high doses, though standard heartworm preventive doses are generally safe — consult your vet)
Milbemycin (found in some heartworm preventives)
Selamectin — use with caution
Moxidectin (found in some heartworm preventives and mange treatments)
Loperamide (Imodium) — an over-the-counter antidiarrheal that can cause severe neurological toxicity

Chemotherapy agents:

Vincristine, vinblastine, doxorubicin — dose adjustments needed in affected dogs

Sedatives and anesthetics:

Acepromazine — can cause prolonged sedation
Butorphanol — potential for prolonged effects

Antifungal agents:

Ketoconazole — P-gp inhibitor that can increase drug levels

Other:

Cyclosporine — requires monitoring
Some cardiac medications

Inheritance and DNA Testing

MDR1 follows a autosomal incompletely dominant pattern — meaning dogs with one copy have some reduced P-glycoprotein function, and dogs with two copies have the most significant deficiency.

DNA test results:

Normal (N/N) — Two normal copies. Full P-glycoprotein function. No increased drug sensitivity.

Carrier (N/MDR1) — One normal, one mutant copy. Somewhat reduced P-glycoprotein. Moderate sensitivity. Many vets recommend treating these dogs with the same caution as affected dogs for high-risk medications.

Affected (MDR1/MDR1) — Two mutant copies. Minimal P-glycoprotein. Highest sensitivity. Avoid all P-glycoprotein substrate drugs at standard doses.

Why Breeders Must Know This

For breeders of herding breeds and their mixes:

Test your breeding dogs — Know the MDR1 status of any dog you breed. Breeding two affected dogs produces all affected offspring.
Inform puppy buyers — Buyers of any herding breed should be told about MDR1, given their puppy's test results, and counseled to inform their veterinarian.
Include MDR1 status on health certifications — Many reputable breeders now include MDR1 results alongside OFA and DNA health panels.
Consider breeding away from the mutation — While eliminating MDR1 from heavily affected breeds like Collies is extremely difficult without sacrificing genetic diversity, breeders can reduce affected homozygous (MDR1/MDR1) offspring by avoiding breeding two affected dogs together.

What Veterinarians Should Know

If your dog is MDR1 affected or a carrier, tell every veterinarian — including emergency vets, specialists, and anyone who may prescribe medication — before any treatment. A medical alert tag noting MDR1 status is a worthwhile precaution.

Washington State University's Veterinary Clinical Pharmacology Lab has published and maintains updated lists of drugs and recommended dosing adjustments for MDR1-affected dogs at their website.

Summary

The MDR1 (ABCB1) mutation disables the blood-brain barrier's P-glycoprotein pump, allowing certain drugs to accumulate to toxic levels. It is most prevalent in herding breeds, especially Collies and Australian Shepherds. Dogs with two copies are at greatest risk; carriers have intermediate sensitivity. Test all herding breed dogs, inform puppy buyers of results, disclose status to all veterinarians, and avoid breeding two affected dogs together. This is life-saving information — not optional knowledge.