I want to start with the phone call I still get occasionally, even now, from owners who’ve just been told their dog has the MDR1 mutation. The panic in their voice is real. They’ve been reading online forums and they’ve concluded their dog is essentially unanageable — that every trip to the vet is a life-threatening gamble.
It isn’t. The MDR1 mutation is important, genuinely important, but it’s manageable. The dogs that get into serious trouble are almost always the ones whose owners or vets don’t know about the mutation, not the ones where it’s known and taken into account.
Let me explain what’s actually going on.
What MDR1 Does
MDR1 stands for Multi-Drug Resistance 1 gene. It codes for a protein called P-glycoprotein, which is a drug transporter found in the lining of the gut, kidneys, liver, and — most relevantly — the blood-brain barrier.
In a normal dog, P-glycoprotein acts as an active pump, shuttling certain drugs back out of cells before they can accumulate to toxic levels. In the brain, this means drugs that reach the blood-brain barrier are actively pumped back out before they can penetrate the central nervous system in significant amounts.
Dogs with the MDR1 mutation produce non-functional P-glycoprotein. The pump doesn’t work properly. Certain drugs that should be kept out of the brain cross the barrier freely and accumulate there. The result can be neurotoxicity — ranging from wobbliness and dilated pupils to seizures, coma, and death in severe cases.
The mutation is a deletion — a small section of the gene is missing. Dogs can carry one copy of the mutation (heterozygous, one normal gene and one mutant) or two copies (homozygous, both genes mutant). Homozygous dogs are significantly more sensitive to affected drugs than heterozygous dogs, though both need care.
Which Breeds Carry It
The MDR1 mutation is almost exclusively a herding breed problem. It arose from a single ancestor, almost certainly a Collie-type dog, and spread through the herding breed population from there.
Breeds commonly affected:
Rough and Smooth Collie: Up to 70% of the breed carries at least one copy in some populations. The highest rates of any breed, which makes sense given they’re probably the source.
Australian Shepherd: Around 50% carrier rate in population studies. The most commonly tested breed in my experience, which reflects good owner awareness.
Shetland Sheepdog: Significant carrier rates, though somewhat lower than Collies.
Border Collie: Carrier rates generally lower than the above — around 5–10% in studies — but the breed is numerous enough that affected individuals are common in absolute terms.
German Shepherd: Low but not zero. Worth testing in any GSD requiring drugs on the affected list.
Belgian breeds: The Malinois, Tervuren, and Groenendael all have reported cases. Less systematic testing in these breeds, so carrier rates aren’t well characterised.
Various other herding breeds — Old English Sheepdogs, English Shepherds, McNabs — also carry the mutation. When in doubt with any herding type, test.
The Drug List
This is the critical practical information. Not every drug is affected. The mutation causes problems only with specific drugs that are normally pumped out by P-glycoprotein. Here are the main ones every herding breed owner needs to know.
Ivermectin. This is the one that put MDR1 on the map. Ivermectin is used as an antiparasitic — in heartworm prevention products and in treatments for mange and other parasitic conditions. At the doses used in most modern dog heartworm preventatives, even homozygous MDR1 dogs are usually safe. The problems historically came from off-label use at high doses (particularly treating mange with products meant for large animals) or from border collies accidentally accessing livestock dewormers. Modern veterinary heartworm prevention at labelled doses is generally safe even in MDR1-affected dogs, but discuss this explicitly with your vet rather than assuming.
Loperamide (Imodium). Available over the counter for human use. It’s used sometimes in dogs for diarrhoea, but it’s a classic problematic drug for MDR1 dogs. A dose that would settle a human stomach can cause profound neurological problems in a homozygous affected dog. Do not give Imodium to a herding breed without checking with your vet first.
Acepromazine. The sedative used in many veterinary procedures. MDR1-affected dogs can have exaggerated responses, particularly prolonged and deeper sedation. Your vet should know about MDR1 status before any procedure involving this drug.
Butorphanol. An opioid pain relief medication. Deeper effects in MDR1-affected dogs.
Vincristine and other chemotherapy agents. If your dog ever needs chemotherapy, MDR1 status is critical information for the oncologist. Several commonly used chemotherapy drugs are affected, and dosing adjustments may be needed.
Selamectin (Revolution/Stronghold). Used in parasite prevention. At standard doses, generally considered safe even in MDR1 dogs, but worth flagging to your vet.
Milbemycin oxime. Another antiparasitic. MDR1-affected dogs should be tested at lower doses first.
The key principle: when any new drug is prescribed for your herding breed, specifically ask whether MDR1 status is relevant. A knowledgeable vet will already be factoring this in; asking the question ensures it doesn’t get missed.
Testing: How and Why
Testing your dog is simple and I’d argue it should be routine for any herding breed. The test requires either a cheek swab or a blood sample. Several commercial laboratories offer it, and the cost is modest — typically between thirty and sixty pounds in the UK.
The result tells you whether your dog is:
- MDR1 Normal: Two normal copies. Standard drug protocols apply.
- MDR1 Heterozygous (Normal/Mutant): One copy of the mutation. Increased sensitivity to affected drugs, though usually less than homozygous dogs. Caution warranted.
- MDR1 Homozygous (Mutant/Mutant): Two copies of the mutation. Highest sensitivity. Full protocol modifications needed for affected drugs.
Once you have the result, the relevant information to keep accessible:
- Note it in any puppy records or transfer documents
- Inform your regular vet and ensure it’s on the dog’s clinical record
- Mention it at any out-of-hours or emergency consultation where the regular record may not be accessible
- Keep a note of it in whatever you use for medical records — a physical card in the dog’s kit bag is not a bad idea for working dogs that may be injured away from home
The importance of this information in emergency situations is significant. If your dog is hit by a car or has a sudden illness and is treated by an unfamiliar vet, that vet needs to know. The drug protocols for an emergency may include drugs that are problematic for MDR1-affected dogs. I’ve seen this cause serious harm; I’ve also seen owners with an MDR1 card in their pocket hand it over at the emergency surgery and have the veterinary team modify their approach accordingly. The second outcome is the one you’re planning for.
Day-to-Day Life With an MDR1 Dog
For most day-to-day veterinary care, the MDR1 mutation changes relatively little. Vaccinations are unaffected. Most routine medications are unaffected. The dog doesn’t need to avoid activities, doesn’t need a special diet, doesn’t need a different lifestyle.
Where it does come in is worming and parasite prevention. This requires a bit more care. Your vet should be selecting parasite prevention products that are safe for MDR1-affected dogs — this usually means avoiding high-dose ivermectin and choosing alternatives with better safety profiles in affected animals. This is straightforward in practice once everyone knows the dog’s status.
Anaesthesia and sedation warrant extra care. Make sure any practice that sedates or anaesthetises your dog has the MDR1 status on record. Protocol modifications exist and are well-established in veterinary anaesthesia; a vet who’s aware will make appropriate choices.
The gut can add complexity. Herding breeds already have a tendency toward digestive issues, and the MDR1 gene is expressed in the gut as well as the blood-brain barrier. Some MDR1-affected dogs have slightly unpredictable drug absorption, which can complicate management of gut conditions. Being transparent with your vet about the MDR1 status helps them interpret any unusual drug responses.
MDR1 and Breeding
This is a contentious area and I want to be careful about how I characterise it.
The responsible breeding position is clear: breeding two affected dogs together should be avoided because it risks producing homozygous affected offspring. The ethical argument is that intentionally producing highly drug-sensitive dogs when you could have produced normal or heterozygous dogs is indefensible.
The more contested question is whether MDR1-affected dogs should be bred from at all. Given the high carrier rates in some breeds — 70% in some Collie populations — strict exclusion of all carriers would dramatically restrict the gene pool. Most breed health committees have therefore taken the position that breeding one carrier to one clear dog is acceptable, as this produces offspring that are either clear or carrier (not homozygous), and that over generations, carrier rates should decline through selection.
This kind of nuanced, evidence-based approach to health testing decisions is what I find most credible in breed health management. The question isn’t just “does this dog have the mutation?” but “how do we use this information to improve the breed’s health over time without damaging genetic diversity?” These are exactly the kinds of considerations that thoughtful breeders engaging with health clearances properly should be working through.
The Information Is Power
MDR1 is not a death sentence for your dog. It’s a management consideration. Dogs with the mutation live full, active, healthy lives — working, competing, being excellent companions — as long as their owners and vets know about it and make appropriate choices.
The danger is ignorance. The dog that arrives at an out-of-hours surgery, owner frantic, no medical records available, and receives standard drug protocols that happen to include high-dose opioids or acepromazine — that dog is at genuine risk.
Test your herding breed. Keep the result accessible. Tell your vet, every vet. It’s not complicated, and it costs almost nothing to get right.
The alternative is finding out the hard way, and in my experience, nobody who’s been through that would choose it.