Most inherited conditions that a dog DNA test looks for are diseases. The MDR1 mutation is different. A dog that carries it can be perfectly healthy all its life, until it is given one of a handful of common medicines at a normal dose and reacts with tremors, drooling, disorientation or worse. Knowing a dog's MDR1 status in advance lets the veterinarian choose a different drug or adjust the dose. This guide explains what the gene does, which breeds are affected and how the test result is used.
Key facts
- MDR1 (also called ABCB1) codes for P-glycoprotein, a pump that keeps many drugs out of the brain and helps the body excrete them.
- The canine mutation is a 4-base-pair deletion that leaves the dog without working P-glycoprotein (Mealey et al., 2001).
- It is most common in herding breeds: Washington State University estimates about 70% of Collies and 50% of Australian Shepherds carry it.
- Loperamide (Imodium) should be avoided in MDR1 dogs; several other drugs need dosing advice. Mixed breeds can carry the mutation too.
What the MDR1 gene does
The MDR1 gene (multidrug resistance 1, now usually named ABCB1) carries the instructions for P-glycoprotein. This protein sits in the cell membranes of the blood-brain barrier, the intestine, the liver and the kidneys and actively pumps certain molecules back out. In practice it does two jobs: it limits how much of a drug reaches the brain, and it helps move drugs out of the body through bile and urine.
In 2001 Katrina Mealey and colleagues at Washington State University showed that ivermectin-sensitive Collies carry a deletion of four base pairs in this gene. The deletion shifts the reading frame, so the cell produces a short, non-functional protein. Without the pump, drugs that are normally kept out of the brain can build up there and cause neurological signs. The OMIA record for the variant describes the inheritance as incompletely dominant: dogs with two copies are the most sensitive, and dogs with one copy can show an intermediate effect.
Breeds that carry the mutation
A breed-history study by Neff and colleagues (2004) traced all copies of the mutation back to a dog that lived in Great Britain before the herding breeds were formally recognized in the 1800s, which explains why it is concentrated in collie-type and related breeds. Washington State University's veterinary pharmacology program, which developed the original test, publishes approximate frequencies based on the dogs it has tested:
| Breed | Approximate frequency |
|---|---|
| Collie | 70% |
| Australian Shepherd and Miniature Australian Shepherd | 50% |
| Long-haired Whippet | 50% |
| McNab, Silken Windhound | 30% |
| Chinook | 25% |
| English Shepherd, Shetland Sheepdog | 15% |
| German Shepherd, herding-breed crosses | 10% |
| Old English Sheepdog, mixed breeds | 5% |
| Border Collie | under 5% |
OMIA also lists the White Swiss Shepherd and the Waller among breeds in which the variant has been reported. The figures above describe the share of tested dogs that carry at least one copy, and they will differ between countries and lines. Mixed-breed dogs are less likely to carry the mutation, but WSU notes that it does turn up in dogs with no obvious herding ancestry, including a Saint Bernard mix identified after a drug reaction.
Reading an MDR1 test result
The test is a simple DNA test, usually from a cheek swab, and laboratories report three genotypes:
- Normal/normal: no copy of the mutation. The dog has normal P-glycoprotein and no MDR1-related drug sensitivity.
- Mutant/normal: one copy. The dog may react to some drugs at higher doses and passes the mutation to about half its puppies on average.
- Mutant/mutant: two copies. The dog lacks working P-glycoprotein and is the most likely to react to affected drugs at normal doses.
Because the genotype does not change, the test only needs to be done once. It is worth recording the result in the dog's veterinary file and telling any new clinic, including emergency services.
Medicines that need care
WSU keeps a list of problem drugs that includes only medicines with peer-reviewed evidence, and it updates the list as research appears. In its current guidance:
- Avoid: loperamide (Imodium). At doses used for diarrhea it causes neurological toxicity in MDR1 dogs.
- Ask for dosing advice: acepromazine, apomorphine, butorphanol, several chemotherapy drugs (doxorubicin, vinblastine, vincristine, vinorelbine), cyclosporine, grapiprant, maropitant and ondansetron.
- Considered safe at label doses: many parasite preventives, including heartworm products containing ivermectin, milbemycin, moxidectin or selamectin and the isoxazoline flea and tick products. The problems with ivermectin arise at the much higher doses used for some other conditions, or when livestock formulations are given to dogs.
This is a general summary, not prescribing advice. Only your veterinarian can decide which drug and dose suits your dog, and the list changes over time. If your dog is in an at-risk breed and has not been tested, tell the vet before any sedation, anesthesia, chemotherapy or antidiarrheal treatment.
Signs of a reaction
The signs of drug toxicity in an MDR1 dog are neurological: drooling, unsteady walking, tremors, dilated pupils, apparent blindness, disorientation, excessive sedation, and in severe cases seizures or coma. If a dog shows any of these after a new medicine, contact a veterinarian or an emergency clinic immediately.
MDR1 and breeding
Because the mutation is common in some breeds, excluding every carrier from breeding would shrink the gene pool sharply. Many breed clubs instead recommend testing all breeding dogs and planning matings so that puppies are less likely to inherit two copies, while also weighing other health and diversity goals. The guide to the coefficient of inbreeding explains why the size of the breeding population matters. Genoscoper's news piece on popular sire syndrome discusses the same trade-off.
Frequently asked questions
Can cats have the MDR1 mutation?
Yes. A different ABCB1 mutation has been described in cats, and WSU states it is found in about 4% of cats. WSU runs a separate test for cats.
Is ivermectin always dangerous for MDR1 dogs?
No. The low ivermectin doses in heartworm preventives are considered safe at label doses. The risk comes from high doses, such as those used to treat mange, or from livestock products. Always follow your veterinarian's advice.
Does a normal/normal result mean my dog can take any drug?
It means the dog has no MDR1-related sensitivity. Other drug reactions, allergies and interactions are still possible, as in any dog.
Do I need to repeat the test?
No. A dog's genotype does not change, so one reliable test is enough. Keep a copy of the result.
Sources
- Washington State University, College of Veterinary Medicine: Program in Individualized Medicine (MDR1 testing) and the MDR1 in dogs page (breed frequencies and problem medications), Washington Animal Disease Diagnostic Laboratory.
- Mealey KL, Bentjen SA, Gay JM, Cantor GH (2001). Ivermectin sensitivity in collies is associated with a deletion mutation of the mdr1 gene. Pharmacogenetics 11:727–733.
- OMIA, University of Sydney: Multidrug resistance 1, ABCB1-related (dog).
- Neff MW, et al. (2004). Breed distribution and history of canine mdr1-1Δ, a pharmacogenetic mutation that marks the emergence of breeds from the collie lineage. PNAS 101:11725–11730.