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MDR1 Gene Mutation

Posted by lhvs on October 29, 2013

Have you heard of the MDR1 gene? If you haven't don't worry not too many people have. MDR1 gene or multi-drug resistant drug gene genetically predisposes many herding-type dog breeds to adverse drug reactions. The drug sensitivies result from a mutation in the MDR1 gene. The most severe reactions occur with the use of many antiparasitic agents (dewormers) like ivermectin. The mutated gene does not allow the brain to pump out drugs like a normal dogs brain would. Reactions can range from extreme and extended sedation to neurological toxicity. These reactions can be extremely serious requiring extended hospital stays or even death.

This gene is most commonly found in herding breeds but can also be found in other breeds of dogs. The highest risk breeds are Collies and Australian Shepherds. See table to the right with breeds and frequency.

The good news is that Washington State University has developed a very simple test for the MDR1 mutant gene. All that is needed for the test is a a swab of the inside of the cheek. The sample can be sent directly to the Washington State University Lab by the owner. Test kits can be purchased online by owners as well. Testing is the only way to be 100% sure if your dog does or does not have the gene. It is always better to be safe than sorry when using any medication or anesthetics on your pets.

Information gathered from www.vetmed.wsu.edu/depths-VCPL/   visit this site for more information or to order a test kit.














Breeds affected by the MDR1 mutation (frequency %)

Breed            Approximate Frequency

Australian Shepherd                     50%
Mini Australian Shepherd            50%
Border Collie                               < 5%
Collie                                             70%
English Shepherd                          15%
German Shepherd                         10%
Herding Breed Cross                     10%
Long-haired Whippet                    65%
McNab                                           30%
Mixed Breed                                   5%
Old English Sheepdog                    5%
Shetland Sheepdog (Sheltie)         15%
Silken Windhound                         30%


Drugs that have been documented to cause problems in dogs with the MDR1  mutation include:

Acepromazine (tranquilizer and pre-anesthetic agent). In  dogs with the MDR1 mutation, acepromazine tends to cause more profound and  prolonged sedation.

Butorphanol (analgesic and pre-anesthetic agent). Similar  to acepromazine, butorphanol tends to cause more profound and prolonged sedation  in dogs with the MDR1 mutation.

Emodepside (Profender?)-is a  deworming drug approved for use in cats only in the U.S., but is approved for  use in dogs in some other countries.  Use of this drug in dogs with the MDR1  mutation has resulted in neurological toxicity.

Erythromycin. Erythromycin may cause neurological signs in  dogs with the MDR1 mutation.  A mutant/mutant collie exhibited signs of  neurological toxicity after receiving erythromycin.  After withdrawal of the  drug, the dogs neurological signs resolved.  There were no other potential  causes of neurological toxicity identified in the dog.

Ivermectin (antiparasitic agent). While the dose of  ivermectin used to prevent heartworm infection is SAFE in dogs with the mutation higher doses, such as those used for treating mange will cause neurological toxicity in dogs that  are homozygous for the MDR1 mutation (mutant/mutant) and can cause toxicity in  dogs that are heterozygous for the mutation (mutant/normal).

Loperamide (ImodiumTM;  antidiarrheal agent). At doses used to treat diarrhea, this drug will cause  neurological toxicity in dogs with the MDR1 mutation. This drug should be  avoided in all dogs with the MDR1 mutation.

Selamectin, milbemycin, and moxidectin (antaparasitic agents). Similar to ivermectin, these drugs  are safe in dogs with the mutation if used for heartworm prevention at the  manufacturer's recommended dose.  Higher doses have been documented to cause neurological  toxicity in dogs with the MDR1 mutation.

Vincristine, Vinblastine, Doxorubicin (chemotherapy  agents). it appears that dogs with  the MDR1 mutation are more sensitive to these drugs with regard to their  likelihood of having an adverse drug reaction. 

 collected from www.vetmed.wsu.edu/depts-VCPL/