Understanding the ABCB1 Gene Mutation:
What Pet Owners Need to Know About Drug Sensitivity in Certain Dog Breeds
Did you know that some dogs carry a genetic mutation that makes them highly sensitive to commonly used medications? If you have a herding breed like a Collie or Australian Shepherd, this is especially important information for you.
This blog explores the ABCB1 gene mutation (formerly known as MDR1) — what it means, which dogs are at risk, and how veterinarians safely work around this mutation to provide appropriate medical care.
What Is the ABCB1 Gene Mutation?
The ABCB1 gene, once commonly referred to as the MDR1 gene, encodes a protein called Pglycoprotein (P-gp). This protein plays a vital role in protecting the brain by pumping certain drugs and toxins out of the brain and back into the bloodstream. It helps maintain what’s known as the blood-brain barrier — a natural defense mechanism that shields the brain from potentially harmful substances.
In dogs with a mutation in the ABCB1 gene, the function of P-glycoprotein is reduced or absent. As a result, certain drugs that would normally be kept out of the brain can accumulate there, leading to exaggerated or even toxic effects.
Breeds at Risk
The ABCB1 mutation is most common in herding breeds and their crosses. Dogs that are most frequently affected include:
- Collies (Rough and Smooth)
- Australian Shepherds
- Shetland Sheepdogs (Shelties)
- Border Collies
- Old English Sheepdogs
- English Shepherds
- German Shepherds (some lines)
- Longhaired Whippets
- Silken Windhounds
- Mixed breeds with herding ancestry
It’s important to note that even dogs who appear unrelated to these breeds may carry the mutation — especially if they have unknown or mixed lineage.
What Are the Risks?
Dogs with the ABCB1 mutation may experience severe side effects to a variety of drugs that are otherwise considered safe for dogs without the mutation. Symptoms can include:
- Disorientation
- Tremors or seizures
- Blindness
- Loss of muscle control or balance
- Coma
- Prolonged sedation
These reactions can be life-threatening if not promptly recognized and treated.
High-Risk Medications
Some of the most significant drug classes that can cause problems in ABCB1-mutant dogs include:
- Opioids (e.g., Butorphanol, Apomorphine): Can cause exaggerated and prolonged sedation or neurologic side effects.
- Macrocyclic lactones (e.g., Ivermectin, Milbemycin, Selamectin): Common in heartworm preventives and anti-parasitic medications. Safe at standard preventive doses, but high doses (like in livestock dewormers) are dangerous.
- Chemotherapeutics (e.g., Vincristine, Doxorubicin): Increased risk of toxicity due to poor drug clearance from the brain and body.
Other medications, such as Metoclopramide (used for nausea) and Cerenia (Maropitant), are also known to interact with P-glycoprotein. These may not be contraindicated but should be used with caution and close monitoring in sensitive dogs.
A Real-Life Example
A recent case sited in veterinary literature involved a Collie with the ABCB1 mutation who was treated with Butorphanol, a commonly used opioid for pain and sedation. Although a standard dose was used (0.2 mg/kg), the dog experienced severe neurologic side effects requiring reversal. The team transitioned to a much lower continuous infusion and used additional medications to prevent nausea and vomiting, and Keppra, an anti-seizure medication, for supportive care.
Interestingly, Butorphanol has not yet been formally classified as a P-glycoprotein substrate through pharmacokinetic studies, but clinical signs repeatedly suggest it behaves like one in ABCB1-mutant dogs. This reinforces the importance of understanding not just what a drug is theoretically supposed to do — but how it actually behaves in the real world with genetically sensitive patients.
Diagnosing the ABCB1 Mutation
Genetic testing is the only way to confirm whether a dog carries the ABCB1 mutation. A simple cheek swab or blood sample can be submitted to a veterinary diagnostic lab for analysis.
Washington State University (WSU) is one of the leading centers for ABCB1 mutation testing and research. Their website provides detailed information for pet owners and veterinarians, and they offer reliable genetic testing services.
How Do Veterinarians Manage ABCB1-Mutant Dogs?
Knowing a dog has the ABCB1 mutation allows veterinarians to tailor medication choices, doses, and monitoring. Strategies may include:
- Choosing alternative medications that don’t rely on P-glycoprotein for metabolism or excretion.
- Using lower doses of certain drugs and titrating slowly while monitoring for signs of toxicity.
- Avoiding certain medications entirely when safer alternatives exist.
- Hospital monitoring after sedation or anesthesia to ensure the pet recovers safely.
- Critical thinking and planning for long-term management — especially when chronic conditions or cancer treatment is involved.
Why This Matters
The ABCB1 mutation is just one example of how genetics can influence medical care. Awareness of this mutation is vital not only for avoiding potential drug toxicity but also for making informed decisions when it comes to sedation, anesthesia, or treating chronic illness.
At Tufts VETS, we remain committed to individualized patient care. Understanding your pet’s unique genetic background allows us to deliver safer, more effective treatments. If you have a breed at risk — or if you simply want to be proactive — talk with your veterinarian about testing and safe medication planning.
Final Thoughts
Whether it's a routine treatment or an emergency, knowledge of the ABCB1 mutation can be life-saving. If your dog is one of the breeds listed — or a mixed breed with herding traits — consider genetic testing and let your veterinary team know the results. It's a simple step that can make a big difference in how we care for your pet.
Have questions? Our team at Tufts VETS is always here to help you navigate genetic testing (which can be done at home), drug safety, and the best care for your pet.