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Multi-Drug Resistance

The Multi-Drug Resistance Gene (MDR) is responsible for removing some drugs from the brain. In Collies, the common MDR1 mutation causes a defect in the P-glycoprotein that transports these drugs, meaning it cannot transport the toxins away and they build up, which can cause among other neurological symptoms - tremors, coma, and can be fatal.

Dogs homozygous for the mutant MDR1 gene have the sensitivity to the drugs involved, and dogs that are heterozygous (one copy of the mutation) still can react at higher doses, as well as passing the gene on to offspring in both cases.

DRUGS LIST
The following are drugs that have been reported to cause this issue in dogs with the mutant gene (list is taken from the laboratory Animal Genetics):

 

  • Ivermectin (found in heartworm medications)

  • Loperamide (Imodium over the counter antidiarrheal agent)

  • Doxorubicin

  • Vincristine

  • Vinblastine (anticancer agents)

  • Cyclosporin (immunosuppressive agent)

  • Digoxin (heart drug)

  • Acepromazine (tranquiliser)

  • Butorphanol ("Bute" pain control)

  • Ondansetron

  • Domperidone

  • Paclitaxel

  • Mitoxantrone

  • Etoposide

  • Rifampicin

  • Quinidine

  • Morphine



GENETIC TEST
A genetic test is available to detect the mutant gene.


Dogs that are homozygous for the mutant gene (MDR / MDR) have two copies will always pass a copy onto offspring, and will display the sensitivity. Carriers, or MDR / n dogs (heterozygous) can also display the sensitivity so it is advised to AVOID the drugs in the list. Clear dogs with the genetic result n / n can never pass the mutant gene onto offspring.

The below chart is a theoretical breeding calculator for the mutant MDR gene. Results in bold are results where the puppy can display the drug sensitivities (affected and carrier dogs). Results that are 'around' a percentage means that each puppy has the quoted percentage chance of that result. It does not mean that EXACTLY that percentage of the litter will have the result. 
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RESULTS IN PRACTICE
Although it can seem like the most ethical thing to do would be to never breed from affected dogs, erasing the majority of the gene pool would have a devastating result (please see Genetic Diversity section). Instead, ensure your breeding stock is tested, and work towards eliminating the condition with subsequent generations of dogs. 

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