MDR1 – Multi-Drug Resistance Mutation in Dogs

A mutation is a change in the DNA sequence of an organism. It can be humans, animals, birds, or any other living organism on this planet. Mutations can result from errors in DNA replication during cell division, exposure to mutagens, or a viral infection. Most of them are not harmful, but some can even lead to cancer. More and more dogs are now being affected by inherited genetic disease mutations. There are now several hundred naturally occurring inherited canine diseases.A mutation that lies near a gene called IFG1 is the one that causes the differences in sizes among dogs. From chihuahuas to Great Danes, dogs differ more in size than any other mammal species on the planet. Surprisingly, a mutation behind such variation has been traced to ancient wolves. The largest breeds are up to 40 times bigger than the smallest.Mutations are not only responsible for changes and differences in sizes but also several health conditions. And MDR1 is one of them.

Multi-Drug Resistance Mutation – MDR1

A change in the animal’s genetic code is called a mutation. The term multi-drug resistance mutation 1 refers to a specific one that occurs at a gene called, as the name suggests, MDR1. It is also known as the ABCB1 gene. What this mutation does is that it makes the animals more sensitive to the side effects or the negative effects of a drug when administered. These effects on a normal animal would actually be severe, but the ones suffering from MDR1 tend to be more affected by the effects.

A protein known as p-glycoprotein is what is coded by the gene MDR1. And this protein was originally discovered in cancer cells. The research showed that when chemotherapy was performed, these cells affected by MDR1 were resistant to it as compared to other cancer cells. It was then discovered that it was this protein, p-glycoprotein, which sat on the walls of the cells like a bouncer outside clubs and pumped the chemotherapy drugs out of the cell, restricting them from entering and curing cancer. The protein is not bad for the body. In normal people, it acts as an entry barrier for chemicals and possible toxins from the cell. Its main function is to protect the brain. It helps keep drugs and chemicals in the bloodstream from entering the brain.

In the process of protection, it ends up making the body more resistant to the medications. In fact, there are cases when two functional copies of the MDR1 gene have been found. In such cases, a normal p-glycoprotein system helps makes animals more resistant to the effects of common medications. This means that they would require higher levels of anti-seizure medications than animals with one or two mutated copies of the gene.

MDR1 in Dogs

When there are mutated copies of MDR1 genes found in dogs, the p-glycoprotein that is produced is abnormal. And without a proper functional p-glycoprotein system, drugs can reach higher levels within the cell as there is no bouncer guarding the doors of the cells. And this is what makes the dogs more sensitive toward certain drugs. The defective p-glycoproteins also allow higher levels of drugs to enter the brain, which in return increases the neurologic effects of some medications.

How does MDR1 in Dogs work on drugs?

The MDR1 drug mutation demonstrates its most significant effects at the level of the blood-brain barrier. In dogs with this mutation, the filtering mechanism in the brain, which protects certain blood-borne substances from entering brain tissues, is absent.

Drugs like Milbemycin, Selamectin, and Ivermectin are commonly used against parasites in dogs. They form a basic ingredient in the heartworm preventives for most canines. When given low doses of the same, it is safe for dogs even with an MDR1 condition. But at high doses, ivermectin can cause neurologic effects in dogs with the MDR1 mutation. Loperamide is another example of a drug that does not cause any harm to normal dogs, but when used on dogs with MDR1 conditions, it can trigger some neurological effects. Sedatives and chemotherapy drugs are other examples of a different reaction for dogs with MDR1 condition as against the ones without. The doses will have to be altered accordingly.

Causes of MDR1 in Dogs

Each Dog inherits two copies of the MDR1 gene – one copy from each parent. If a dog inherits a defective copy of the gene from each parent, the lack of normal p-glycoprotein production will lead to signs of MDR1 mutation. The degree of severity will depend on the number of abnormal gene from the parents. A dog with only one abnormal MDR1 gene may show milder and less severe symptoms as compared to a dog with two of those.

Which Dog breeds are prone to MDR1?

It is a common observation that the development of this gene is seen mostly in herding breeds. The percentage of chances can differ from breed to breed. Some examples of the same are as follows –

There are other breeds as well which are affected by the condition. They include Longhaired Whippet, McNab Shepherd, Shetland Sheepdog, Silken Windhound, Rough Collie, Smooth Collie, American White Shepherd, etc.

Clinical Signs and Symptoms MDR1 in Dogs

The abnormal MDR1 gene will lead to the development of toxins in the brain, which will then lead your Dog to show some neurological symptoms. These include –

Note: An MDR1-induced seizure could trigger an epileptic seizure as well.

Treatment of MDR1 in Dogs

The following is the list of drugs that should be avoided for all the herding dogs or the ones with the condition –

Apart from this, when any of the signs of MDR1 gene mutation are spotted, it is recommended that you consult your vet immediately since the course of other medical treatments will have to be changed completely. Unfortunately, there is no cure for MDR1 drug sensitivity.

Conclusion

MDR1 is a gene mutation that occurs in canines and makes drug reception more effective than necessary, which in turn causes more sensitivity to the side effects as well. There is no anecdote available as of now to prevent it from happening as it is purely a gene-related disease. Signs should be looked for, especially if your Dog is a herding dog or a Collie. Maintain regular visits to the vet, and the harmful impacts can be limited by changing the course of medications.

Happy Mood and Health to your Dog, and lots of Love and Licks to you!