What is the multidrug resistance mutation (ABCB1 or MDR1)?
A mutation is a change in an animal’s genetic code. A specific mutation that occurs at a gene called ABCB1 (or MDR1) is known as a multidrug resistance mutation.
Animals with a mutation of this gene are more likely to experience severe side effects to several medications, including certain dewormers (at high doses), loperamide (an antidiarrheal agent), some sedatives and opioids, and several anticancer medications. Affected dogs may require lower doses of these medications compared to unaffected dogs to reduce the chance of side effects, or your veterinarian may recommend avoiding them completely.
Herding breeds (collies and Australian shepherds) are more commonly affected by this mutation, although any dog can be affected. A similar ABCB1 mutation can also occur in cats, although it is believed to be much less common. Cats with this mutation may also be unusually sensitive to certain medications.
How does the ABCB1 (MDR1) mutation make animals more sensitive to medication?
The ABCB1 (MDR1) gene produces a protein known as p-glycoprotein. This protein acts as a pump in cells, helping to clear chemicals and potential toxins from the cell. P-glycoprotein plays an especially significant role in the blood-brain barrier that helps keep drugs and chemicals in the bloodstream from entering the brain.
- Animals with two functional copies of the ABCB1 (MDR1) gene have a normal p-glycoprotein system, which helps make them more resistant to the effects of medications.
- Animals with two mutated copies of the ABCB1 (MDR1) gene have abnormal p-glycoprotein and a non-functional p-glycoprotein system, which makes them more sensitive to the effects of certain medications.
How do drug effects differ in animals with ABCB1 (MDR1) mutation?
The most significant effects of the ABCB1 (MDR1) drug mutation are seen at the blood-brain barrier. The term “blood-brain barrier” describes a filtering mechanism that keeps certain blood-borne substances from entering the brain tissue. In pets with the ABCB1 (MDR1) mutation, defective p-glycoproteins allow higher levels of drugs to enter the brain, increasing the neurologic effects of some medications.
Ivermectin and related drugs (milbemycin, selamectin) are commonly used in the prevention and treatment of parasites. They are common components of most canine heartworm preventives. At low doses, such as those used in heartworm prevention, ivermectin is safe even for pets with the ABCB1 (MDR1) mutation. However, at high doses, such as those used in treating parasites such as demodectic mange, ivermectin can cause neurologic effects in dogs with the MDR1 mutation.
Eprinomectin, an antiparasitic drug used in some feline heartworm preventives, can cause severe side effects even at lower doses and is not recommended for cats with known mutations. Other heartworm preventive medications appear to be well tolerated if administered as recommended.
Loperamide (Imodium®) is another drug with potential neurologic effects in dogs with the ABCB1 (MDR1) mutation. This drug does not affect the brain in most dogs, due to p-glycoprotein’s ability to pump the drug out of the brain. Dogs and cats with the ABCB1 (MDR1) mutation, however, can experience neurologic effects from loperamide.
Sedatives, such as those commonly given as components of a balanced anesthetic protocol (acepromazine, butorphanol), may also show stronger effects in dogs and cats with an ABCB1 (MDR1) mutation. In these pets, there is a higher degree and duration of sedation. These pets may still receive typical anesthetic drugs safely, but veterinarians may avoid them or use lower doses.
Chemotherapy drugs may trigger more severe side effects in pets with ABCB1 (MDR1) mutation. These effects can include gastrointestinal toxicity and bone marrow suppression, even at low doses.
How do dogs or cats develop an ABCB1 (MDR1) mutation?
The ABCB1 (MDR1) mutation involves a deletion of certain base pairs in the pet’s genetic code. This deletion results in the protein coded by this gene, p-glycoprotein, being abnormal. Pets inherit two copies of the MDR1 gene – one copy from each parent.
- If a pet inherits two defective genes (a defective copy from each parent), the lack of normal p-glycoprotein production will lead to signs of ABCB1 (MDR1) mutation.
- If a pet inherits only one abnormal ABCB1 (MDR1) gene, they may show mild effects, but they will be less severe than in a pet with two abnormal copies of the gene.
What is the likelihood that my pet is affected by the MDR1 mutation?
The MDR1 mutation is most seen in herding dog breeds. The effects of the mutation vary in severity, depending on whether the pet carries one or two copies of the mutation. Affected dog breeds include:
- Collies (70%)
- Australian shepherds (50%)
- Shelties (15%)
- Border collies (5%)
- English shepherds (15%)
- German shepherds (10%)
- Old English sheepdogs (5%)
- Mixed breed (5%)
- Silken windhound (30%),
- Long-haired whippet (50%)
Unfortunately, it is not as easy to recognize potentially affected cats. There are no cat breeds associated with higher incidence of ABCB1 mutation. It is estimated that up to 4% of cats in the U.S. population are affected.
How can I know if my pet has an MDR1 mutation?
There is a commercially available test that assesses blood samples (or a cheek swab) for the presence of the ABCB1 (MDR1) mutation. Ask your veterinarian about this test, especially if your dog is a herding breed or if you suspect an ABCB1 (MDR1) mutation in your pet.
