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As an englishman, I’m used to fielding questions about my homeland, but earlier this year, my jaw dropped when a patient asked me, “Who’s Kate Middleton?” It amazed me that anyone could be unaware of the future king of England’s bride. I couldn’t help thinking, How did you manage to avoid this story? Where have you been hiding? Little did I know that my next patient, a three-year-old Australian Shepherd named Cyrus, would show me how easy it is to be uninformed.
“He’s been lame in his front right for about five months,” his owner, Jaime, told me. “It gets worse with exercise.” The symptoms seemed consistent with a shoulder injury. It may be a sweeping generalization, but problems involving toes, wrists and elbows — hinge joints — tend to reveal themselves with pain, swelling or an abnormal range of motion. Ball-and-socket joints, like the shoulder, rely a little more heavily on muscles, tendons and ligaments for stability, which makes the shoulder vulnerable to repetitive sports injuries. Throw in this breed’s innate desire to exercise, and you have a recipe for low-grade, niggling lameness.
“I’d like to sedate Cyrus, get some ultrasonographic images of his shoulder joint and, if indicated, give him a steroid shot.”
Jaime agreed, and we set a date for the imaging. Later, when she dropped off Cyrus, she gave me a printout she thought I would appreciate. Hidden in Cyrus’s record, I discovered a document stating that he carried two copies of the mutant MDR1 gene, and a list of the dozens of drugs (including most sedatives) that would be seriously detrimental to his health.
Where had I been hiding? I read the information as though I were a green veterinary student struggling to assimilate important new stuff. What was the MDR1 gene? Did I miss that lecture? Surely Cyrus was not the first blue merle Aussie I had seen since graduating more than 22 years ago.
It turns out I was not completely ignorant. I recalled warnings about the mysterious sensitivity of Collies and related breeds to a variety of drugs, especially the anti-parasitic ivermectin. Not so long ago, the reason behind this sensitivity was discovered: the multi-drug resistance gene (MDR1) codes for a protein integral to pumping a variety of drugs from the brain back into the blood.* Dogs who carry two mutant MDR1 genes (mutant/mutant) lack this all-important protein, which means that many drugs can linger in the brain and cause life-threatening side effects. Even dogs with only one normal copy of the gene (mutant/normal) can be more vulnerable to drug toxicity.
The MDR1 mutat ion notably affects Collies — roughly three out of four Collies in the U.S. carry mutant MDR1 — Longhaired Whippets, Shelties, Aussies and Old English Sheepdogs. (Washington State University’s website provides a comprehensive list of drug susceptibilities and instructions for having your dog’s DNA tested  via a blood sample or cheek swab; ) Naturally, I wondered why I had never witnessed adverse drug reactions in any of the listed dog breeds whom I had cared for in the past. Could I just have been lucky and only had normal/normal dogs?
When I asked my colleagues in anesthesia, they gave me the same withering look I had dispensed so easily only days earlier. Of course they knew about MDR1, and altered dosages and chose drugs accordingly. Sedatives can be used safely if the dose is reduced by 25 to 50 percent. Perhaps this was the answer. Maybe my natural proclivity for using the lowest possible dose to achieve sedation had inadvertently prevented dangerous side effects.
As for Cyrus, despite his genetic anomaly, his procedures went well; the suspected tendon injury was confirmed and he responded nicely to the steroid injection. There were no problems with his sedation, unless you count the professional embarrassment I felt for not knowing about his DNA. The good news was that this dog reminded me that I cannot possibly know everything, that I must be receptive to learning and that I am grateful for others who know so much more than I.
More importantly, it’s going to be a while before I think any question is too dumb to ask.
*Mealey K.L., et al., “Ivermectin sensitivity in Collies is associated with a deletion mutation of the MDR1 gene,” Pharmacogenetics 11, no. 8 (2001): 727–33.