Genetics

MDR1 Mutation

A mutation in the ABCB1 gene causing multi-drug resistance protein 1 deficiency. Affected dogs cannot adequately pump certain drugs out of the brain, leading to neurological toxicity at standard doses.

The MDR1 mutation (now formally called ABCB1 mutation) affects the gene encoding P-glycoprotein — a drug efflux pump in the blood-brain barrier that removes many drugs from the central nervous system. Dogs homozygous for the mutation (mutant/mutant) have severely impaired drug efflux; heterozygous dogs (normal/mutant) have partial impairment.

Affected Breeds

The MDR1 mutation arose in a single ancestor of the collie lineage and spread through related herding breeds:

BreedApproximate Frequency
Rough Collie70% carry at least one copy
Australian Shepherd50%
Shetland Sheepdog15%
Border Collie5%
German Shepherd10%
English Shepherd~15%
McNab~30%

Also found in mixed breeds with herding ancestry.

Dangerous Drug Classes

Dogs with MDR1 mutation develop neurological signs (ataxia, tremors, hypersalivation, seizures, coma, death) at doses safe for normal dogs. Key drug categories:

Antiparasitics: ivermectin, milbemycin, moxidectin, selamectin (at high doses used for demodectic mange), loperamide (not a parasite drug but affected)

Chemotherapy agents: vincristine, vinblastine, doxorubicin — normal chemotherapy doses can be fatal in affected dogs

Others: acepromazine (sedation), butorphanol, digoxin — variable risk

Standard heartworm prevention doses of ivermectin (6 µg/kg) are safe even in mutant/mutant dogs. The toxicity risk is with high-dose ivermectin used for other parasites.

Management

DNA testing confirms mutation status. Every MDR1-affected dog should have mutation status documented in their veterinary records. Before any prescription:

  1. Alert the prescribing veterinarian
  2. Veterinarian consults the Washington State University VCPL drug list
  3. Dose adjustments or drug substitutions are made as needed

This information should be clearly marked in the dog’s medical record and communicated at every veterinary visit.