MDR1: Multi Drug Resistance Gene

MDR1 is a mutant gene that occurs in some breeds which affects the canine's ability to pump certain systemic drugs out of the brain. Without this ability, drugs can reach toxic levels causing neurological symptoms. Sometimes these symptoms are mild and other times the symptoms are severe enough to lead to coma and death

What worries me as much as the serious reactions are the less obvious signs that something isn’t right. Signs that may be overlooked but that may cause a Sheltie to feel ill without my being aware. I want real health for my guys not just the absence of disease.

Your dog may start showing drooling, irritability, ataxia…. things you would not immediately think of as a drug reaction.

And while it has been stated that it is only the higher doses of drugs that cause a reaction in Shelties with MDR1, I have to respectfully disagree.  (That’s me; always picking a fight.)

 My feeling is that it is possible for the drug to slowly build up in the body and brain over time with continuous low dosing such as monthly heartworm preventatives. At some point the “tipping point” would be reached and the result would become toxic.

That’s just me and my paranoia talking.

So far I have been lucky enough to have all my Shelties normal. But if I did own a Sheltie that had MDR1, I would watch him like a hawk for ANY mild signs that a drug was affecting him or her over time. 

What Breeds Carry MDR1?

Herding breeds are the most common with collies having the highest incidence at about 75% of the population. Shelties fortunately are only around 15%. There are other herding breeds, as well as mixed breeds that possibly carry MDR1 as well.

It is a paired gene, one inherited from the sire, one from the dam. Which means that a Sheltie can have any one of these combinations of the Multi Drug Resistance Gene:

  • Normal/Normal
  • Normal/Mutant
  • Mutant/Mutant

Initially, I thought that the Normal version of the gene was dominant. That would mean that a Sheltie with the combination Normal/Mutant would be, in effect, a “carrier” but normal in behavior, able to take the suspect drugs without toxicity. 


The MDR1 normal gene is an incomplete dominant. Meaning, if a Sheltie has a Normal/Mutant combination, it is possible he or she may become toxic from the drugs; But then again, maybe not.

I really do prefer things in black and white, but that’s not life, is it?

I also used to think the only drug to be concerned about was ivermectin which is a common heartworm medication and switching to another medication like Interceptor would solve any problems.

BUZZZZZZZ! Wrong again!

Don’t ask me why the phrase “MULTI-DRUG” never sank in as, DUH! Lots of drugs can cause a problem…

What Drugs Affect A Canine With MDR1?

The following medications are the ones that can cause a toxic reaction at normal dose. Some can “safely” be given at a lower dose: 

  • Acepromazine
  • Butorphanol
  • Doxorubicin
  • Emodepside
  • Erythromycin
  • Ivermectin
  • Loperamide
  • Selamectin
  • Milbemycin
  • Moxidectin
  • Vincristine
  • Vinblastine
  • Doxorubicin

There are other drugs that, even though they are known to be pumped out of the brain by  this gene, are for some reason, tolerated by pups with mutant gene.

A more complete explanation of MDR1 and each drug can be read on the Washington State University College of Veterinary Medicine site.

How Does This Affect Breeding?

If you breed a dog that is Normal/Mutant with a bitch that is Normal/Normal the odds are (over time and a statistically significant number of litters) that 75% of the pups will be normal and 25% with be Normal/Mutant.  So a decision has to be made if the Normal/Mutant dog has other qualities that outweigh the possibility of producing other carrier puppies.

If you breed a dog that is Normal/Mutant with a bitch also Normal/Mutant you raise the odds to 50% of producing pups with Normal/Mutant genes.

Increasing the number of Mutant genes in each parent increases the chances of affected puppies. 

All my breeding stock is tested unless clear by parentage, so I know what I have to deal with.  All prospective puppy buyers are given the information about parents of each litter.

How Can I Find Out If My Puppy Is Affected?

Anyone can get their puppy tested at any time. It is a DNA test. A simple cheek swab sent to PawPrint Genetics is all it takes. That and $80 (There is a discount if you do multiple DNA tests on your dog.)

MDR1 testing
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