Canine Multidrug Resistance (MDR1) Gene: Keeping Your Dog Safe When They Need Medical Help

What is MDR1 in dogs?

Multidrug resistance (MDR1) is a gene that is responsible for the production of a protein called P-glycoprotein (P-gp). The protein is present in healthy tissues with secretory/excretory functions such as the liver, kidney, and intestine, as well as the capillaries of the brain.  When properly functioning, the protein helps in the elimination of drugs, chemicals, and toxins from the body into bile, urine, and intestine. Additionally, at the blood-brain barrier, P-gp restricts the drugs from entering the central nervous system. It is well understood that the protein has a protective function by eliminating potentially toxic xenobiotics from the body and preventing their entry into the brain and organs of reproduction.^1,2

Given its crucial physiological role, loss of function of P-glycoprotein via germline mutation in the MDR1 gene is known to cause the heritable disease, Multidrug sensitivity. This can lead to severe and potentially fatal adverse drug reactions in some dog breeds. For example, MDR1 gene mutation is associated with increased susceptibility to neurotoxic side effects of several drugs including ivermectin, moxidectin, and loperamide. More details on those drugs later.^3,4

Thankfully, because MDR1 is an error in genetic code, it is possible to identify it in a patient before adverse reactions are exhibited. Furthermore, MDR1 is easily navigated when its presence is known by the pet parent and veterinarian providing care. When a vet knows that the MDR1 gene is present, they are able to make educated treatment decisions. These include avoiding the more commonly used drugs known to cause reactions in dogs with the gene and switching them with less common drug substitutions. As well as, using drugs at a lowered dosage than would be given to a dog without the gene. Regardless of which medications are used, your veterinarian will closely monitor your pet’s progress and modify medications and dosages as needed to keep your pet safe during treatment.^1,2,3 

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When and why should you test your dog for MDR1?

MDR1 can cause some serious drug toxicity side effects in a patient who is treated without knowledge of the gene’s presence. Common side effects of drug toxicity in dogs with MDR1 include vomiting, weakness, lack of coordination, lethargy, tremors, seizures, blindness, and death. For some of the more manageable side effects, a vet may be able to diagnose the patient with MDR1 just from the reaction. However, knowing that the symptoms can include death, it is safer for your dog if you and your vet know prior to treatment that they have the MDR1 variant. 

Because MDR1 is a genetic abnormality, dog breeds create an easy indicator that a pet parent should have their dog tested for the gene. Herding dog breeds are more likely to have the gene and it is highly recommended to have them tested for it.^{1,2,3,4,5,6,7} 

The way that genes are passed from a parent dog to a puppy allows for a few different ways that the MDR1 gene can manifest. The lesser of these is if the dog has a mutation in only one of the two copies of the gene; this scenario means that the reaction caused by the anomaly is less intense.  On the other side, a dog that has two copies of genes with MDR1 mutation is more highly susceptible to the effects of drug toxicity, and will definitely require a closer observation when taking any medications. Any representation of the gene in the body will make a difference in the way that the dog should be treated when it comes to medications.

What breeds are affected by the MDR1 gene?

Herding breeds are the most likely to carry the MDR1 gene, and if your dog is a mixed breed with one of the herding breeds listed below, it may be beneficial to get them tested for the gene as well. 

1. Standard Collies

• ‍‍Purebred collies have ~75% chance of carrying the mutation 

2. Australian Shepherds

• ~50% are affected by at least one copy of the gene

3. Mixed breeds of herding dogs

• Up to 35% chance of being affected by at least one copy of the gene, depending on what breeds they are mixed with 

4. Shetland Sheepdogs

• ~10% chance of being affected

5. German Shepherds, Border Collies, English Shepherds, and Old English Sheepdogs 

• Less than 5% chance of being affected. 

If your pet is a mixed breed with an unknown heritage, having them tested for the MDR1 gene would be beneficial in the long run. Remember that it only takes one copy of the gene for it to affect how your pet will respond to any medications. 

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What does having the MDR1 gene mean for dogs with cancer?

MDR1 mutation leads to adverse reactions to drug treatments, and many cancers in dogs are effectively treated with multiple chemotherapy drugs. These two details in combination make for a complicated treatment plan, especially in dogs that have not yet had the MDR1 gene status identified. 

There are several drugs known to have an effect on the MDR1 gene, and care should be taken to avoid prescribing them to dogs with the condition.⁷ 

Some of those drugs can be found in:

1. Ivermectin, Selamectin, Milbemycin, Moxidectin

• Parasite preventatives such as heartworm medications
• All FDA-approved heartworm medications are safe for dogs with the MDR1 gene. Though it is safest if your vet verifies if a heartworm medication has too high of a dosage for a dog with the MDR1 gene.

2. Acepromazine, Butorphanol

• Commonly used sedatives 
• still can be used, though in significantly lower dosages

3. Loperamide

• Gastrointestinal medication
• Used to limit vomiting and diarrhea

4. Vincristine, Vinblastine, Doxorubicin, Paclitaxel

• Cancer medications
• Including chemotherapy treatments and other non-chemotherapy medications

If a dog that has been diagnosed with cancer also has the MDR1 gene mutation, or even if the dog has the potential to have the mutation, choosing the right treatment plan for them and the right combination of medications is imperative to their safety and health. 

Knowing that a canine cancer patient may have adverse reactions to some of the more commonly used drugs due to the presence of the MDR1 gene mutation can lead to finding a more efficient and effective method for treating it safely. 

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ImpriMed gives every dog a fighting chance against lymphoma

ImpriMed has been pushing the boundaries of what veterinary oncology can do for its patients. ImpriMed has already advanced the way that canine lymphoma is treated through the use of a live sample of the patient’s cancer cells, AI technology, and an ever-growing database about canine lymphoma treatments. By creating the Personalized Prediction Profile, ImpriMed has helped vets find the best treatment options for individual patients based on how their cancer cells react to different drugs and dosages of chemotherapy medications. 

Now, we’re taking it one step further and will be offering an MDR1 gene test as well. This can be done alone or as an add-on with any of our services, especially with the Personalized Prediction Profile to help narrow down the safest and most effective treatment for that patient. Adding the MDR1 test is highly recommended for herding breeds with lymphoma. 

Find out more about the Multidrug Sensitivity Genotyping (MDR1) through ImpriMed

Learn about drugs that may interact poorly with MDR1 gene here.

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