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MDR1 Gene Mutation

*Important Info for Australian Shepherds and Many Herding Breeds

What is MDR1?

MDR1 is the abbreviated name of a gene called Multi-Drug Resistance 1. A mutation of this gene causes sensitivity to Ivermectin and a number of other drugs. Dogs with the mutation will react to those drugs. Having two copies of the mutation will lead to drug reactions, but having a single copy can also cause some sensitivity with some drugs.

Dogs with this mutation have a transport defect - the drug goes in to their brains, fails to be transported out, and builds up to toxic levels. This causes serious neurological problems including seizures and sometimes death.

The most commonly affected breeds come from the herding class. Approximately three of every four Collies in the United States have the mutant MDR1 gene. The frequency is about the same in France and Australia, so it is likely that most Collies worldwide have the mutation. The MDR1 mutation has also been found in Shetland Sheepdogs (Shelties), Australian Shepherds, Old English Sheepdogs, English Shepherds, German Shepherds, Long-haired Whippets, Silken Wind hounds, and a variety of mixed breed dogs.

Testing a Dog for the MDR1 Mutation is Easy:

You can order a testing kit by contacting the Veterinary Clinical Pharmacology Laboratory at Washington State University: www.vetmed.wsu.edu/vcpl or by phone 509-335-3745.

The only way to know if an individual dog has the mutant MDR1 gene is to have the dog tested. As more dogs are tested, more breeds will probably be added to the list of affected breeds.

 

Breeds affected by MDR1 mutation (frequency %)

Breed and Approximate Frequency

Australian Shepherd 50% Australian Shepherd, Mini 50

Border Collie < 5% Collie 70 %

English Shepherd 15 % German Shepherd 10 %

Herding Breed Cross 10 % Long-haired Whippet 65 %

McNab 30 % Mixed Breed 5 %

Old English Sheepdog 5 % Shetland Sheepdog 15 %

 

Please follow these easy instructions to assure the safety of your new fur-family member:

  1. After reading this article, please visit the web site suggested for testing and learning more about MDR1 Gene Mutation.

  2. Make a copy of these pages for your veterinarian office to keep in your dog’s folder. It is impossible for our vets today to be aware of every issue each breed has to offer. It is your job as a responsible pet owner to make sure your vet has this information each time your dog visits the vet office. Only use a veterinarian that is willing to avoid the drugs on the MDR1 DO NOT USE list. Always question your vet before administering drugs either orally or through a shot that they are not drugs listed on the DO NOT USE list in your dog’s folder at each vet visit, as a reminder.

  3. Make a copy for each of your vehicles that your dog may be traveling in. That way, in case of an emergency away from home where an emergency vet visit is necessary, you can reach your MDR1 information for your breed and inform an emergency vet of the DO NOT USE list for this breed. Not every vet is fully informed on MDR1. Remember to put the originals back in your folder for safe keeping after making your copies.

  4. Decide if you are going to test your dog. There is testing information on the previous page. You can also search your web browser for additional options for testing. If you choose to not test, then you must avoid the drugs on the DO NOT USE list. Some owners choose to not use the drugs even with a clear test just to be safe. Remember you must do one or the other, or both for the safety of your pet.

  5. Visit with your vet and familiarize yourself with alternative drugs that are commonly used. For example: Most breeds use HEARTGUARD for heart worm prevention. It is recommended that our breed use INTERCEPTOR instead. It’s as simple as exchanging one drug for another, double checking the DO NOT USE list before administering any drugs to your Aussie, and making sure your vet follows the guidelines.

  6. Remember to always leave a copy of the DO NOT USE list with boarding kennels, family and friends when someone else is taking care of your dog in case of an emergency.

 

Drugs that have been documented to cause problems in dogs with the MDR1 mutation include:

  • Ivermectin (antiparasitic agent)- While the dose of ivermectin used to prevent heartworm infection is (supposedly) SAFE in dogs with the mutation (6 micrograms per kilogram), higher doses, such as those used for treating mange (300-600 micrograms per kilogram) will cause neurological toxicity in dogs that are homozygous for the MDR1 mutation (MDR1 mutant/mutant) and can cause toxicity in dogs that are heterozygous for the mutation (MDR1 mutant/normal).

  • Selamectin, milbemycin, and moxidectin (antaparasitic agents)- Similar to ivermectin, these drugs are safe (again...supposedly) in dogs with the mutation if used for heartworm prevention at the manufacturer’s recommended dose. Higher doses (generally 10-20 times higher than the heartworm prevention dose) have been documented to cause neurological toxicity in dogs with the MDR1 mutation.

  • Loperamide (ImodiumTM; antidiarrheal agent)- At doses used to treat diarrhea, this drug will cause neurological toxicity in dogs with the MDR1 mutation. This drug should be avoided in all dogs with the MDR1 mutation.

  • Acepromazine (tranquilizer and pre-anesthetic agent)- Based on collaborative research, the VCPL has determined that dose reductions are required for dogs MDR1 mutant/mutant and MDR1 mutant/normal.

  • Butorphanol (analgesic and pre-anesthetic agent)- Dose reduction required for dogs MDR1 mutant/mutant and MDR1 mutant/normal.

  • Chemotherapy Agents (Vincristine, Vinblastine, Doxorubicin, Paclitaxel)- Based on collaborative research, the VCPL has determined that dose reductions are required for dogs MDR1 mutant/mutant and MDR1 mutant/normal in order to avoid SEVERE toxicity.

  • Apomorphine - this drug is used to induce vomiting in dogs that have ingested poisons/toxins. It can cause central nervous system depression in dogs with the MDR1 mutation at standard doses.

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