Article: Canine Multidrug Sensitivity (MDR1)

MDR1 (Multi-drug sensitivity) & the Australian Shepherd

Many breeds of dogs these days have genetic issues.  The Australian Shepherd, along with others in the herding breeds, has a genetic issue, which as a dog owner, you may wish to know more about.  It is the MDR1 gene mutation.  The MDR1 or Multi-Drug Resistance Gene issue is one that is shared by the Australian Shepherd, Border Collies, Collies, English Shepherds, Long-haired Whippet, McNab Shepherds & BCs, Old English Sheepdogs, Shetland Sheepdogs, Silken Windhounds, Rough & Smooth Collies, German Shepherds, Bobtails, American White Shepherds.

The Multi-Drug Resistant Gene (MDR) codes for a protein that is responsible for protecting the brain by transporting potentially harmful chemicals away from the brain.  In certain breeds, a mutation occurs in the MDR1 gene that causes sensitivity to certain anesthetics and drugs.  Dogs with this mutation have a defect in the P-glycoprotein that is normally responsible for  transporting certain drugs out of the brain.  The defective protein inhibits the dog’s ability to remove certain drugs leading to a buildup of these toxins and as a result of the accumulation of toxins, the dog can show neurological symptoms, such as seizures, ataxia or even death.  When you purchase a puppy within the above breeds, you may have your pup tested for the MDR1 gene mutation.  In fact, when or if you purchase your puppy from a reputable breeder, you may ask for a copy of the sire and dam’s tests given to them prior to breeding.  While a number of breeders may feel that the MDR1 issue is not important and may not test for it in their own breeding animals, the fact is, you could be purchasing a puppy which carries a genetic issue towards this defect.  There are three categories in which this test results will fall:  N/N, for normal/normal, which means the dog has not inherited the MDR1 issue; M/N, for mutant/normal, which means that both normal and mutant copies of the gene is detected and thus the dog is a carrier for the MDR1 mutation and M/M for mutant/mutant meaning that the dog or bitch carries two copies of the mutant gene and is homozygous for the MDR1 mutation.  This dog will react to Ivermectin, Butorphanol, Ketamine, Loperamide, Doxorubicin, Vincristine, Vinblastine, Cyclosporin, Digozin, Acepromazine and so on.  Read the links below to learn more about this potentially serious issue in the herding breeds of dogs.

My own personal experience with this issue came as a result of a reaction in our first Aussie, Geordie, a rescue, who at the age of nine had been attacked by two dogs and required an operation to repair the damage to his hindquarters. Although he had had two previous anaesthetics, this time he was administered Butorphanol and Ketamine.  Not knowing much about the MDR1 issue and not being aware that he could possibly be sensitive to these drugs, I was surprised when he reacted to the drugs.  The vets had difficulty pulling Geordie out of the anesthetic, which upset and worried them and the next day Geordie began to hallucinate.   His body had spasms of trembling and he began to turn his head wildly from side to side, eyes unfocused, which lasted well over a week following his operation.  He was frightened as was I.  When these episodes passed, he was never quite the same dog after that.  His energy seemed diminished, his playfulness, diminished and it was then that I determined that any further Australian Shepherd pup I would purchase would be tested for the MDR1 gene mutation.

Some breeders will test for the MDR1 gene mutation prior to breeding their sire or dam, some do not.  Some will openly list this under the sire and dam’s lineage and test results, which is what one would hope for but not all breeders accept that the MDR1 gene mutation is serious enough to be considered in not passing this on through the next generation of puppies.  It is wise to ask a herding dog breeder if they have had their animals tested for the MDR1 issue.   If they do not test for this in their breeding animals, ask why.  Educate yourself on this genetic issue for not all are affected as you will note above depending on the sire and dam’s genetic history.  In our two present Aussies, Annie, (Thornapple Aussies, MI) is M/N.  Meg, (Stonehaven/Bayshore, MD & W.VA). is M/M.  The recommended anesthetic for Meg & Annie, both, is:  Isoflurane.  The relaxant used on both prior to an operation is: Propofol or Diprivan.  Neither have had any reaction to these drugs.

DISCOVERY OF THE MDR1 Gene Mutation:  Dr. Katrina Mealey of Washington State University, College of Veterinary Medicine discovered, through her research in pharmacogenetics, the MDR1 gene mutation in herding dogs and its implications for multi-drug sensitivity. The conclusion through her research is that all dogs carrying the MDR1 gene mutation are descendents of canines who lived in Great Britain as far back as the Celts/Picts/Scots and the Australian Shepherd is believed to share a common ancestry with collies, suggesting that the MDR1 mutation might stem from a single ancestral mutation that has been inherited identical by decent. It was the introduction of Ivermectin in the early nineteen-eighties, an anti-parasitic drug that uncovered a preexisting mutation in dogs that predisposed them to a potentially fatal neurotoxicosis reaction. It is caused by a defect in the blood brain barrier and MDR1 sensitive dogs are not able to express drugs out of their brains. In addition to the drug, Ivermectin, there are other drugs which affect MDR1 canines.

For further study, please consult “Breed Distribution and History of Canine MDR1, a pharmacogenetic mutation that marks the emergence of breeds from the collie lineage” at: http:www.pnas.org/search?fulltext=MDR1=herding=dog=gene=mutation&submit=yes

And check out the following links:
(1) ASHGI MDR1 FAQs page: http://www.ashgi.org/articles/mdr1.htm

(2) In Canada: Health Gene Laboratory, Toronto: http://www.healthgene.com

(3) In the United States: Washington State University VetMed College:
www.vetmed.wsu.edu/depts-vcpl/test.aspx

(4) Dr. Susan Thorpe-Vargas: http://pawpeds.com/pawacademy/genetics/breedingstrategies

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