MDR1

Many herding breed dogs (the most commonly affected in the UK are: All breeds of Collie, Shetland Sheepdog, GSD and, Australian Shepherd dogs - including cross breeds) have a genetic predisposition to adverse drug reactions involving over a dozen different drugs.

The most serious adverse drug reactions involve several antiparasitic agents, Ivermectin, Milbemycin (and related drugs), the antidiarrheal agent Loperamide (Imodium), and several anticancer drugs (Vincristine, and Doxorubicin, plus several others). These drug sensitivities result from a mutation in the multidrug resistance gene (MDR1 gene).

A test distinguishes between clear, carrier and affected dogs. Clear dogs have no copies of the mutant gene responsible for the condition and will neither develop the condition nor pass the gene on to their offspring. Carrier dogs have one copy of the normal gene and one copy of the mutant gene, they will not develop the condition, but will pass a mutant gene on to approximately half of their offspring. Affected dogs have two copies of the mutant gene that causes the condition, and therefore, will react adversely to certain drugs.

When considering the use of macrocyclic lactones such as ivermectin or moxidectin in dogs, vets have followed the adage, “white feet, don’t treat.” This refers to the known sensitivity of Scotch collies (both rough and smooth) to neurotoxicity when administered these drugs at higher than label doses. But the adage has also been applied to many other herding breeds and has prevented vets from using these drugs in situations where they would have been ideal. The neurotoxicity was attributed to a leaky “blood-brain barrier” in susceptible dogs. Recent developments in the molecular mechanisms of this phenomenon have opened a new frontier in the area of pharmacogenetics — drug disposition determined by the animal’s genotype. So “white feet, don’t treat” is no longer the practice standard; now it is “white feet, test to see if you can treat.”

EXPLANATION OF TEST RESULTS

MDR 1 ARTICLE BY SHARON VANDERLIP RAINSHADE COLLIES HERE

Recognizing that the collies and other herding breeds that were sensitive to ivermectin were similar to the mdr knockout mice, Dr. Katrina Mealey at Washington State University, College of Veterinary Medicine, demonstrated that a deletion mutation of the mdr gene was present in ivermectin-sensitive collies

Test results from Laboklin will automatically be sent to the Kennel Club for inclusion on its database

Results from other laboratories may be included on the database upon owner submission and request – please email hbs@thekennelclub.org.uk for further information.

There are many other drugs that have been shown to be pumped by human P-glycoprotein (the protein encoded by the MDR1 gene), but data is not yet available with regard to their effect in dogs with the MDR1 mutation.