MDR1 Gene Mutation in Dogs: Vet’s 2025 Guide to Drug Sensitivity, Testing & Safe Treatment 🧬🐶 

By Dr. Duncan Houston BVSc

Hello—I’m Dr Duncan Houston BVSc, veterinarian and Ask A Vet founder. The MDR1 gene (also ABCB1) encodes P‑glycoprotein, which helps pump drugs out of the brain and other organs. A mutation here—especially the 4‑base pair deletion—makes some dogs highly sensitive to medications, including ivermectin, sedatives, loperamide, and certain chemotherapy drugs. This vet‑approved guide explains:

• What the MDR1 mutation is and how it affects drug handling
• Breeds most commonly at risk
• Signs of toxicity and drugs to avoid or adjust
• Genetic testing and interpreting results
• Safe medication protocols
• How Ask A Vet tools help safeguard sensitive pups

1. What Is the MDR1 Mutation?

The MDR1 mutation involves a 4-base deletion in the ABCB1 gene, resulting in nonfunctional P‑glycoprotein. This protein normally pumps drugs out of the brain, liver, kidneys, and intestines. Affected dogs cannot eliminate certain drugs efficiently—leading to dangerous accumulation.

2. Which Breeds Are at Risk?

• High frequency: Collies (≈70%), Australian Shepherds (≈50%), Shetland Sheepdogs (≈10–15%)
• Other herding breeds: Border Collies, German Shepherds, Old English Sheepdogs, English Shepherds, McNabs, Wällers, Silken Windhounds, Whippets
• Mixed breed dogs with herding ancestry may carry the mutation.

3. Drug Sensitivities & Toxicity Signs

• Macrocyclic lactones (ivermectin, selamectin, milbemycin): high doses can cause tremors, ataxia, seizures or coma in homozygous dogs.
• Sedatives/analgesics: acepromazine, butorphanol—enhanced sedation; use 25–50% dose reductions or avoid.
• Imodium (loperamide): can trigger severe neurological signs—avoid in all MDR1 dogs.
• Chemotherapy: agents like vincristine, vinblastine, doxorubicin—risk of extra toxicity; reduce doses and monitor closely.
• Other drugs: erythromycin, ketoconazole, digoxin, cyclosporine—adjust or avoid as needed.

4. Recognizing Toxicity

• Clinical signs: tremors, coordination loss, salivation, seizures, disorientation, respiratory arrest.
• Onset depends on drug’s metabolism but signs typically appear within hours to days.
• Supportive care includes IV fluids, anticonvulsants, temperature control, and hospitalization.

5. Genetic Testing & Result Interpretation

Testing is done via cheek swab or blood sample:

• N/N (normal): standard drug protocols are safe.
• N/M (carrier): variable sensitivity—clinically mild; use reduced doses and monitor.
• M/M (affected): high sensitivity—even low doses can be toxic; avoid or significantly reduce doses.

6. Safe Treatment Strategies

• Always test before using high-risk drugs, especially in herding breeds.
• Prefer MDR1-safe alternatives (e.g., fipronil instead of ivermectin for ectoparasites).
• Consult vet pharmacology guidelines (WSU list) for dosing adjustments.
• Monitor neurologic signs closely post-medication.

7. Ask A Vet Tools for Medication Safety

• Log genotype result (N/N, N/M, M/M) for reference.
• Track all medications, dates, doses and any adverse effects.
• Set reminders for reduced-dose schedules and lab monitoring.
• Receive alerts if high-risk drugs are added to a pet’s profile.

📌 Final Thoughts from a Vet

The MDR1 mutation affects P‑glycoprotein function, making many herding dogs sensitive to commonly used medications. With genetic testing, tailored dosing, and safe alternatives, these dogs thrive without risk. Ask A Vet helps track genotype, prescriptions, and alerts—so every treatment is a safe one. 🧬🐾❤️