Some dogs are more prone to serious side effects from taking medications than others, due to an MDR1 gene mutation. You may have heard of MDR1-related drug sensitivity in Collies, but did you know that it can occur in other breeds too? This includes mixed breeds! So, how do you know if your dog has an MDR1 mutation? Let’s take a look at all you need to know. 

What is the MDR gene? 

MDR stands for ‘multidrug resistance’. It is also known as the ABCB1 gene. A ‘mutation’ means a change in the genetic code. Dogs which have a mutation, or change, in the MDR1 gene are more likely to experience serious side effects from certain types of medication. These side effects occur at the dose of medication usually given to dogs, so are not related to over-dosing.  

How does the MDR1 gene affect dogs? 

The MDR1 gene is responsible for coding (in other words, they contain the instructions for the production of) P-glycoprotein, a type of protein involved in removing chemicals from cells, via a ‘cell pump’. P-glycoproteins are very important in the ‘blood-brain barrier’, which prevents potentially harmful chemicals from moving out of the blood stream and into the brain. They also help keep certain chemicals (including drugs) out of the other organs.  

MDR1 gene mutation causes a change in P-glycoproteins, so that the system does not work properly. When dogs have these mutated MDR1 genes, drugs can build up and can cross the blood-brain barrier when usually they wouldn’t. So, dogs with mutated MDR1 genes are at greater risk of serious side effects of certain medications. 

Dogs inherit one copy of the MDR1 gene from each parent. If a dog inherits a mutated gene from both parents, resulting in two defective genes, all of their p-glycoprotein production will be abnormal, leading to signs of MDR1 mutation. If a dog inherits one mutated gene and one normal gene, they may still show signs, but these will be milder, as they are still able to make some normal pumps. 

What are the symptoms of MDR1 related drug reactions? 

The signs of drug toxicity in dogs with MDR1 mutation are usually neurological, meaning relating to the nervous system. Symptoms can include: 

  • Drooling (excessive salivation) 
  • Sickness (vomiting) 
  • A wobbly gait (ataxia)  
  • Weakness  
  • Tremors 
  • Blindness 
  • Seizures 

As well as protecting the brain, the MDR1 gene is very important for removing drugs from the body. Dogs with mutated MDR1 genes can therefore have reduced drug elimination, increasing their risk of toxicity and serious side effects. Sadly, this can even result in death. 

Which dogs are affected by the MDR1 gene mutation? 

The mutated MDR1 gene is most common in herding breeds, especially Collies. MDR gene dog breeds include: 

  • Collie 
  • Australian Shepherds 
  • Long-haired Whippets 
  • Silken Windhound 
  • Shelties 
  • English Shepherd 
  • German Shepherd 
  • Border Collies 
  • Old English Sheepdog 
  • Shetland Sheepdog 
  • McNab Shepherd 
  • Wäller 
  • White Swiss Shepherd 

As only one defected gene is required for problems to occur, cross-breeds can also be affected if one parent carried the mutant gene.  However, the mutation crops up occasionally in other, unrelated breeds too. 

How do I know if my dog has the MDR gene mutation? 

If your dog is a herding breed, or you are worried they have the MDR gene mutation, there are genetic tests available. Your vet may recommend testing if your dog has had an adverse reaction to certain drugs, or they may make a presumptive diagnosis. Testing involves your vet sending a blood test or mouth swab to a laboratory to be analysed.  

It’s a good idea to have the test done if you are considering breeding from your dog and they are an ‘at risk’ breed, since they can pass the mutated gene to their offspring. This can help you decide whether to breed, and if you do breed, to ensure you choose a suitable mate.  

What do the results mean? 

  • Dogs with two normal genes are expected not to have multidrug sensitivity. They cannot transmit a mutated MDR1 gene to their offspring (although of course the other parent could). 
  • Dogs with one normal MDR1 and one mutated gene may show mild to moderate multidrug sensitivity. They will pass the mutated MDR1 variant to half of their offspring. Whether the offspring is then at risk of two mutated MDR1 genes will depend on the other parent. 
  • Dogs with two mutated MDR1 genotypes will have multidrug sensitivity. They will pass the mutated variant to their offspring. 

Your vet will explain what any results mean for your dog. If you are considering testing for your dog, or have any concerns, please speak with your vet in the first instance.  

What is the treatment? 

There is no treatment or cure for MDR1 related drug sensitivity.  

Treatment for drug reactions is symptomatic, meaning your vet will tailor a treatment plan based on the symptoms that your dog is experiencing. This could include intravenous fluid therapy (IVFT, otherwise known as a drip), anti-sickness medication, or anti-seizure medication. 

It’s important to note that not all drug reactions are due to the MDR1 gene – in fact, most probably are due to other factors, such as dose issues, or other genetic pathways that we can’t currently test for. Your vet will be able to advise you if the reaction is likely to be MDR1 related, so you should discuss any concerns you may have with them. 

If your dog is affected (or suspected to be) by the MDR1 mutation, the treatment is using lower drug doses for certain drugs, or avoiding them altogether, to avoid a drug reaction.  

MDR1 in dogs – drugs to avoid 

P-glycoproteins are involved in the absorption, distribution and removal of many drugs. However, only a few of these drugs can cause severe toxicity in dogs with the MDR1 mutation.  

Drugs that should be avoided, or used with caution include: 

  • Ivermectins and other structurally-related drugs (such as milbemycin and selamectin). These are commonly used to treat and prevent parasites.  
  • Loperamide, sometimes used to treat diarrhoea. 
  • Certain sedatives, such as acepromazine and butorphanol.  
  • Chemotherapy drugs. 

Extra care needs to be taken when using combinations of drugs at the same time. Some drugs can increase the concentration of other drugs in the bloodstream, when the medications are used together. This increases the risk of an adverse reaction, even in dogs without the mutation.   

Luckily, you don’t need to worry about which drugs you should or should not use for your dog – your vet will advise you which drugs are safest and at what dose. You should always tell your vet first if you are planning to give your dog any medication, including flea or worm treatment (or even supplements), so they can advise you if it is safe. 

You should never change the dose of, or stop, a medication that has been prescribed by your vet without talking to them first.  

Take home message 

The MDR gene is not just about collies! Many breeds, including cross breeds, can be affected. Dogs with two mutated MDR1 genes are at greater risk of more serious reactions. 

The good news is that MDR1 drug-sensitive dogs can live normal lives, if proper care is taken over both drug doses and the choice of drug. However, dogs may have a serious reaction before it is known they are MDR1 drug-sensitive. Also, some dogs are more sensitive than others, and so side effects may be unexpected or unavoidable.  

Remember, not all drug reactions are MDR related!  

If you have any concerns or questions about your dog, make an appointment with your vet to discuss.  

Further reading 

The pharmacogenomics of P-glycoprotein and its role in veterinary medicine  

Multidrug resistance 1 (MDR1) gene mutation in dogs – The Veterinary Nurse  

DNA Test – MDR1 – The Kennel Club