While collies have the biggest issue with this multi-drug sensitivity -- about 75 percent of them worldwide carry the defective gene -- other herding breeds also are potential victims. Approximately 10 percent of Shetland sheepdogs and Australian shepherds carry the mutant gene. At the opposite end of the spectrum are border collies, with only 1 percent believed to be carriers. [Katrina Mealey] says Old English sheepdogs and German shepherds have a "very low" risk factor, with single-digit carrier rates, although white- factor shepherds -- those that are albinos or produce it in offspring -- are at higher risk.
Ironically, the most well-known source of canine exposure to ivermectin -- heartworm medications such as Heartgard -- poses the least risk for MDR1 dogs. Mealey notes that the ivermectin dose in heartworm preventives is so low -- usually 6 micrograms per kilogram -- "that they are safe once a month, even for dogs with the mutation."
By contrast, when ivermectin is used as a treatment for mange, the typical dose is 300 micrograms per kilogram a day -- more than 50 times the heartworm dose. "That dog will go into a coma" if it has the MDR1 gene, Mealey warns.
Most dog-savvy people -- not to mention their vets -- know about the connection between collies and invermectin. These herding dogs have a heritable sensitivity to the anti-parasitic drug, which can overwhelm the blood-brain barrier, causing neurotoxicity, coma and, sometimes, death.
In 2001, veterinarian Katrina Mealey of Washington State University College of Veterinary Medicine in Pullman, Wash., and her team found that ivermectin sensitivity is caused by a mutation in the multi-drug resistance gene (MDR1), which controls a protein that helps pump drugs and toxins out of the brain.
But as the research continued, the scientists discovered that the gene may react to more than 50 drugs, such as Loperamide (the over- the-counter antidiarrheal Imodium); the popular tranquilizer Acepromazine, often called "Ace" for short; the heart drug Digoxin; pain-control medication Butorphanol; Cyclosporin, an immunosuppressant used in allergy treaments; and several chemotherapy drugs, including Doxorubicin, Vincristine and Vinblastine.
(For a list of other drugs that have the potential to cause problems in dogs with the MDR1 mutation, visit www.vet med.wsu.edu/ depts-VCPL.)
While collies have the biggest issue with this multi-drug sensitivity -- about 75 percent of them worldwide carry the defective gene -- other herding breeds also are potential victims. Approximately 10 percent of Shetland sheepdogs and Australian shepherds carry the mutant gene. At the opposite end of the spectrum are border collies, with only 1 percent believed to be carriers. Mealey says Old English sheepdogs and German shepherds have a "very low" risk factor, with single-digit carrier rates, although white- factor shepherds -- those that are albinos or produce it in offspring -- are at higher risk.
There is a noninvasive test to determine whether a dog is a MDR1 carrier. The $60 test involves swiping the inside of the dog's cheek with a small bristle brush and mailing the DNA in for analysis.
While Mealey's research has been published in several veterinary journals, she says she still fields calls every week from owners whose vets know nothing about this herding-dog-specific sensitivity.
Ironically, the most well-known source of canine exposure to ivermectin -- heartworm medications such as Heartgard -- poses the least risk for MDR1 dogs. Mealey notes that the ivermectin dose in heartworm preventives is so low -- usually 6 micrograms per kilogram -- "that they are safe once a month, even for dogs with the mutation."
By contrast, when ivermectin is used as a treatment for mange, the typical dose is 300 micrograms per kilogram a day -- more than 50 times the heartworm dose. "That dog will go into a coma" if it has the MDR1 gene, Mealey warns.
Another area for concern is avermectins used as pesticide sprays. Mealey recalls a case where a couple took their Labrador retriever and collie to their vacation home, where the grounds had been treated with the ivermectin-like compound.
"A day later, the collie was in a coma and the Lab was fine," she explains. "The veterinarians almost euthanized the dog, thinking it was some bizarre neurological thing. If you're a sensitive dog, the coma can last for weeks until the drug gets out of your system," Mealey says -- a likely death sentence for dogs that have not been properly diagnosed.
Thankfully, the owners' Web surfing turned up the chemical culprit, and after several weeks, the collie emerged from the coma no worse for wear.
Mealey notes that many specialist vets, such as dermatologists treating mange, will recommend that owners of herding breeds conduct the DNA test to see if the dog has the mutation. "Now a lot of oncologists are starting to as well," she adds, because some cancer- fighting agents will cause a similar reaction in high doses. "When you lower the dose of chemo, it decreases the chances of putting a dog into remission" -- a precaution that defeats the purpose of the cancer treatment in the first place.
While some sighthounds such as the silken windhound and long- haired whippet also carry the renegade MDR1 gene, researchers have concluded that the mutation likely found its way into those gene pools through sheepdog crosses made to produce their flowing coats.
As for the gene itself, DNA sequencing of neighboring genes has shown it was a spontaneous mutation that arose in one dog who likely lived in Great Britain in the mid-1800s, before the first herding breeds were even recognized.
This nameless prototypical sheepdog "was a working dog, and probably a good one," Healey explains, " so its genes were passed on" -- for better and worse.
