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Multidrug Resistance Mutation (MDR1) in Dogs and What That Means for Your Pet

Multi-Drug-Resistance-1 (MDR1 or ABCB1) is a gene that the body uses to protect the brain. This is a protein in cell membranes and it is responsible for transporting certain drugs out of brain cells. Put more formally, it is an ATP-dependent efflux pump with broad substrate specificity. If this gene is mutated, it will create a defective protein (ineffective efflux pump), and drugs will remain and build up in the brain to toxic levels. MDR1 is inherited in an autosomal incomplete dominant manner in dogs, meaning that dogs only need to inherit one copy of the mutated gene to be at an increased risk of developing adverse reactions to certain medications. If neither parent has a copy of the mutated MDR1 gene, then the resulting offspring will be clear as well.

The most common breed associated with MDR1 mutation is the Collie, but generally, herding breeds are affected, and that includes any mixed breeds you might find at the shelter. Below is a list of breeds that are frequently affected by the MDR1 mutation.

  • Australian Shepherd

  • Border Collie

  • English Shepherd

  • McNab Shepherd

  • Old English Sheepdog

  • Shetland Sheepdog

  • Silken Windhound

  • Rough Collie

  • Smooth Collie

  • German Shepherd

  • American White Shepherd

  • English Shepherd

There are multiple drugs that will affect dogs with the mutated MDR1 gene. As long as your veterinarian is aware of your dog’s MDR1 status, they are able to consider which drugs are best suited for the current treatment. Those with a Normal/Mutant gene may be less susceptible to these drugs, though they may react to severely increased doses. Below is a list of drugs that should be generally avoided in dogs with an MDR1 status, or herding breeds or mixed breeds of unknown MDR1 status.

  • Ivermectin

  • Selamectin

  • Moxidectin

  • Loperamide

  • Acepromazine

  • Butorphanol

  • Vincristine

  • Vinblastine

  • Doxorubicin

  • Paclitaxel

  • Apomorphine

The following list is drugs that are known to be removed from the brain via the MDR1 gene, but appear to be safely tolerated by dogs with the mutation.

  • Cyclosporin

  • Digoxin

  • Doxycycline

  • Morphine

  • Buprenorphine

  • Fentanyl

Incorrect use of Ivermectin was a catalyst for the first testing of MDR1. The majority of farm dogs are herding breeds. Farmers used to give them high doses of injectable or oral Ivermectin as a dewormer because they were highly susceptible to getting worms by being around livestock. With so many dogs showing adverse reactions, farmers and veterinarians looked for a pattern, which is where the adage ‘white feet, don’t treat’ came from, in reference to the white feet on most herding breeds.

Ivermectin is still used as an effective dewormer in heartworm medications, such as Heartgard Plus (prescription preventative) and those that are sold in veterinary clinics have been tested as generally safe for dogs with the MDR1 mutated gene if used to the manufacturers’ specifications. There are other options for heartworm medication, such as the Interceptor Plus mentioned above, so Ivermectin doesn’t necessarily need to be used. But if following the recommend dosing from the manufacturer there shouldn't be anything to worry about. If your dog is living near livestock, ensure they are not eating any feces or any discarded dewormer. When livestock are given dewormer, it is a high dose of Ivermectin, and it can remain in the feces for an extended period of time. High doses of Ivermectin are still sometimes used for treating mange and should be avoided in any MDR1 status dogs. Dogs with a confirmed MDR1 mutation should generally be limited to milbemycin oxime (Interceptor Plus - prescription preventative) for heartworm prevention. At the dosing manufactured by Interceptor Plus, milbemycin oxime is safe for use in MDR1 dogs. Increased doses can cause issues, however.

If you are looking to purchase one of the breeds listed above, or a mixed breed that appears to have any mixture of the above breeds, see if the breeder has had the puppy or parents tested. A dog only needs to be tested once in its life as its DNA won’t change, and this type of testing for at-risk breeds is something one should expect from an ethical breeder. Breeders should give preference to breeding dogs with Normal/Normal MDR1 status, but simply removing all those that are not Normal/Normal would sometimes deplete the breeding stock of less common breeds to a point that would do more harm than good to the breed as a whole (Silken Windhounds, for example, are still relatively uncommon). If there were not enough dogs to contribute to the gene pool then new genetic diseases or other health issues could become predominant. Therefore, ethical breeders should consider the mutation a fault like any other and weigh it against the other pros and cons of breeding any particular dog. If your breeder has completed the testing on either the puppy or the parents, please be sure you have a copy of the results to give to your veterinarian so they can be treated appropriately. If the puppy has been purchased for showing and potential breeding, MDR1 testing should be considered as important as any other test for that breed.

Anytime you go to a new veterinary practice, ensure the veterinarian knows the dog's MDR1 status. Your veterinarian is the one who should know which drugs are safe and which are not, and in what doses, so that they can make an appropriate plan whenever your dog needs treatment. The MDR1 status can also be taken into account if any neurological signs appear so that the veterinarian can give a correct diagnosis.

If you don’t yet know the MDR1 status of your dog, you may want to consider gene testing. Gene testing with a reputable company that includes health panels is generally quite affordable. Embark Breed + Health is a good one to look into. If you opt for this testing, be sure to give a copy to your veterinarian for your dog's records.



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