MDR1 Gene in Dogs: What You Need to Know
By K9Reproduction.com Editorial Published Apr. 3, 2023
What Is the MDR1 Gene in Dogs?
In 2001, it was discovered that several herding-breed dogs were more likely to have a genetic mutation making them more sensitive to certain medications. This mutation occurs in the MDR1 (multidrug resistance 1) gene, causing a change in an important protective molecule called P-glycoprotein. This molecule helps eliminate medications and other toxic compounds from the dog’s body and prevents these substances from entering places they shouldn’t, like the brain.
Dogs with a mutation of the MDR1 gene (or a defective MDR1 gene), also called the ABCB1 gene, are more likely to have serious side effects from certain classes of medication, such as ivermectin, an anti-parasite drug. Many Collie owners know that ivermectin drugs may be dangerous for their dogs when used at non-FDA approved doses. The MDR1 gene mutation is responsible for this increased risk of toxicity.
But it’s not just Collies, and it’s not just ivermectin. Other breeds and medications are linked as well. As we’ve learned more about genetics, we have developed ways to identify dogs that carry the MDR1 gene mutation and to make better choices in reducing their risks of serious medication side effects.
How Do Medications Affect Dogs With the MDR1 Gene?
In dogs with a defective MDR1 gene, P-glycoprotein does not function properly. Normally, P-glycoprotein acts like a bouncer, keeping medication and toxins out of areas they shouldn’t be in, such as the brain. Additionally, if toxins are found in the liver or kidneys, P-glycoproteins work to eliminate them as bile or urine.
Dogs with a mutation in the MDR1 gene and subsequent changes in P-glycoprotein function are unable to keep some drugs from crossing the blood-brain barrier. When some drugs that are normally considered safe enter the brain, they can cause neurological problems like seizures, blindness, tremors, lack of coordination, and even death. Additionally, these substances cannot be cleared from the body as efficiently, leading to symptoms like drooling, nausea, or prolonged sedation.
Certain drugs, such as ivermectin, that are usually safe for dogs when given at proper doses can become life-threatening when they enter the brain and cause neurological problems.
How Do Dogs Develop the MDR1 Gene?
Mutations in the MDR1 gene are hereditary, meaning the defective gene is passed down from one generation to the next. Dogs inherit an abnormal MDR1 gene from their parents: Every dog inherits two copies of the MDR1 gene, one from each parent. If both copies are mutated, the dog will have drug sensitivity and toxicity. However, even if they inherit one abnormal MDR1 gene, they may still experience drug sensitivity, just less severe.
This condition is inherited, and the offspring of an affected dog will likely also be affected, depending on whether one or both parents carry two copies of the mutated gene. In litters where only one parent was affected, some puppies may carry the genetic mutation while other puppies do not.
What Dog Breeds Have the MDR1 Gene?
The most common breed affected by the mutated MDR1 gene is the Collie, with 70% of tested Collies being affected. Australian Shepherds and Mini Aussies are a close second, with about 50% of tested dogs having the mutated gene. Other breeds reported to carry the trait include:
Collies
Australian Shepherds
Miniature American Shepherds
Shetland Sheepdogs
Old English Sheepdogs
Chinook
German Shepherds
Other herding breeds (e.g., Border Collies, Australian Cattle Dogs)
Medications MDR1 Dogs Should Avoid
Dogs carrying the MDR1 mutated gene are more sensitive to certain medications and more likely to experience a toxic reaction. Always consult your veterinarian before starting any new medication with your pet. Known medications that affect dogs with the MDR1 mutated gene include:
Ivermectin
This common anti-parasite drug is used in many heartworm prevention products and is safe at low, FDA-approved dosages for monthly use, even for MDR1 breeds. However, it should not be given at higher doses used for treating external parasites, like demodectic mange. Consult your veterinarian for safe treatment options.
Loperamide (Imodium)
This anti-diarrheal drug is extremely toxic to dogs with the MDR1 gene mutation and should not be given to any dog or breed likely to carry the abnormal MDR1 gene.
Sedatives
Certain sedative drugs, like butorphanol and acepromazine, may cause toxicity in MDR1 gene dogs. Your veterinarian may dose these lower or avoid them altogether during anesthesia or for sedation during stressful events.
Chemotherapy Agents
Chemo drugs like vincristine and doxorubicin are P-glycoprotein substrates and are slower to be metabolized and cleared by MDR1 dogs. They may result in more side effects. Consult your dog’s oncologist for safe chemotherapy options.
Digoxin
This heart drug has increased toxicity risks in dogs with the mutated MDR1 gene.
How To Determine if Your Dog Has the MDR1 Gene
Genetic testing is readily available to determine if your dog carries the mutated MDR1 gene. Testing can be performed using a simple cheek swab or blood drawn in a veterinary office. Consult your veterinarian about your dog’s breed and recommendations regarding testing. If you do independent testing, provide your vet with a copy of the results to keep your pet’s medical record up to date.
FAQs
Q: What is the MDR1 gene in dogs? A: The MDR1 gene, also known as the ABCB1 gene, is responsible for producing P-glycoprotein, which helps eliminate medications and toxins from a dog’s body. A mutation in this gene can cause increased sensitivity to certain medications.
Q: Which dog breeds are most affected by the MDR1 gene mutation? A: The most affected breeds include Collies, Australian Shepherds, Miniature American Shepherds, Shetland Sheepdogs, Old English Sheepdogs, Chinook, and German Shepherds.
Q: What medications should be avoided in dogs with the MDR1 gene mutation? A: Medications to avoid include ivermectin at high doses, loperamide (Imodium), certain sedatives (butorphanol and acepromazine), chemotherapy agents (vincristine and doxorubicin), and digoxin.
Q: How can I find out if my dog has the MDR1 gene mutation? A: Genetic testing can be done using a cheek swab or blood sample. Consult your veterinarian for testing recommendations.
Q: What are the risks of giving medications to dogs with the MDR1 gene mutation? A: Dogs with the mutation may experience neurological problems, such as seizures and tremors, as well as other side effects like drooling and prolonged sedation.
Understanding the MDR1 gene and its implications can help you make informed decisions about your dog's health and medication needs. For more information, visit K9Reproduction.com.
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