Note that this article is provided for informational purposes only. It is not intended to diagnose or provide veterinary care information. Work with your vet to provide the best possible care for your dog.
If you’ve ever talked to anyone who owns or breeds Collies, you may have heard that Collies are known to be sensitive to Ivermectin – the drug in many heartworm medications. For a long time it has been known that Collies are sensitive to this drug, but no one really knew why. The only option to avoid an adverse reaction was to avoid the drug for all Collies.
Modern technology has shed some light on this issue and also highlighted a potential issue in the German Shepherd breed. Research at the Veterinary Clinical Pharmacology Laboratory at Washington State University’s College of Veterinary Medicine has found the cause of this drug sensitivity in Collies. The problem is a mutation in the Multi-Drug Resistence Gene (MDR1). This gene encodes a protein that is responsible for pumping drugs and other toxins out of the brain. Dogs with the mutant gene cannot pump out some of these drugs which leads to neurological symptoms, as well as in severe cases, coma or even death. Washington State University developed a DNA test with a simple cheek swab to check for the MDR1 mutation.
In identifying the gene, it was determined that approximately 75% of Collies in the US carry the mutation. It’s no wonder than that this is a problem generally thought to be associated with Collies. However, research indicates this mutation can be found in many other breeds, including German Shepherds. In fact the most recent studies show than 10% of German Shepherds are affected by this mutation. This means it is big issue for owners and breeders of German Shepherds and something that should not be ignored.
Research also indicates that Ivermectin is the not only drug that causes a problem. The following drugs have been documented, or are strongly suspected to cause problems in dogs with the MDR1 mutation:
- Ivermectin (antiparasitic agent)
- Loperamide (Imodium®; over-the-counter antidiarrheal agent)
- Doxorubicin (anticancer agent)
- Vincristine (anticancer agent)
- Vinblastine (anticancer agent)
- Cyclosporin (immunosuppressive agent)
- Digoxin (heart drug)
- Acepromazine (tranquilizer)
- Butorphanol (pain control)
The following drugs may potentially cause problems when given to dogs that have the mutation. Biochemical studies have shown that this gene has the potential to act on over 50 different drugs.
- Ondansetron
- Domperidone
- Paclitaxel
- Mitoxantrone
- Etoposide
- Rifampicin
- Quinidine
- Morphine
Mini Aussie Rescue & Support (MARS) has an excellent fact sheet you can download here with details on all the problem drugs.
Since there are so many drugs that may cause a problem, it is important for owners to know about the possibility and have your dog tested if you suspect a problem. It is even more important for breeders to have their breeding stock tested so that the problem can be avoided.
Here is some information on what to do and how:
Step 1: Have Your Dog Tested
You can have your dog tested for the MDR1 mutation using a commercial test available from Washington State University. You can order a test kit online at http://www.vetmed.wsu.edu/depts-VCPL/orders_interface/Results/submission_form.asp or contact the Veterinary Clinical Pharmacology Laboratory at 509-335-3745. The kits are free, but when you return them to the lab, the fee is $ 70 per test. If you do five or more at a time, it’s $ 60 a test. The good news is that the test is simple and you can administer it yourself. There is no need to go to the vet and pay additional charges. The kit will include two brushes which you simply rub on the inside of your dog’s cheek.
Step 2: Interpret the Test Results
Your test results will arrive in about two weeks. You can indicate if you want the results emailed, faxed or mailed to you. When you get the results, your dog will have one of three possible results.
Normal/Normal – This means your dog does not carry the mutation and cannot pass it on to his offspring. The dog should not experience any adverse drug reactions to the drugs listed above.
Mutant/Mutant – This means your dog carries two copies of the mutation. He will pass on a copy of the mutant gene to his offspring. Your dog would be expected to experience toxicity after normal doses of loperamide (Imodium), and some anticancer drugs, and high doses of ivermectin (greater than 50 micrograms per kilogram). Other drugs on the above list should be avoided if possible as they may also cause adverse reactions.
Mutant/Normal – This means your dog carries one copy of the mutation and one copy of the normal gene. He may pass on the mutant gene to his offspring (statistically there is a 50/50 chance). Your dog may experience toxicity after normal doses of loperamide (Imodium®), and some anticancer drugs, and high doses of ivermectin (greater than 50 micrograms per kilogram). Other dogs on the above list may cause a reaction as well.
Step 3: Report Results
OFA (Orthopedic Foundation for Animals) maintains a database of DNA tests on dogs. By submitting your test results to OFA, you are contributing to a database that can be used to eliminate the mutant gene from the German Shepherd breed. To report your test results to OFA, you must fill out the application for the DNA Database which can be found at http://offa.org/pdf/dnaapp_bw.pdf. The fee for OFA submission is $ 15 a dog or $ 7.50 if you submit five or more for Normal/Normal dogs. Affected dogs may be submitted to OFA at no charge.
You will receive a certificate from OFA and an OFA number for each test result.
Here is an example of a GSD with MDR1 test results reported in the OFA database.
Here is an example of what the OFA certificate looks like.
If you tested a white German Shepherd, you should also report the results to the White Shepherd Genetics Project. To do this, go to their web site at http://wsgenetics.org/ and click on “Database Submissionâ€. There is no fee for submitting this information.
Step 4: Provide the Information to your Vet
It’s important to provide your vet with information about the outcome of your tests. This helps him provide the best possible care for your dog. Take a copy of this article or print out the web page http://www.vetmed.wsu.edu/depts-VCPL/ and give it to your vet along with the test results. Talk with your vet and make sure he understands the implications of the test results for your dog.
Also make a copy of your test results and information on what it means as well as the list of drugs and put it somewhere that is easy to carry with you. If you have an emergency and take your dog to a different vet or an emergency clinic, they won’t have access to his records from your regular vet. Some of the drugs on the list are tranquilizers and pain killers – drugs that could easily be given in an emergency situation – so it’s important to have this information on hand.
Mini Aussie Rescue & Support offers an excellent medical alert kit for dogs impacted by the MDR1 mutation. For just $ 5, the kit includes a medical alert tag, warning stickers for the dog’s veterinary file and multiple copies of the problem drug list for you to give to your vet, keep in your purse or wallet, and place in the glove box of your car.
Step 5: Breeding
In terms of the many health issues that can impact our dogs , this is a relatively minor issue. However, it’s still something breeders should consider as just one of the many variables that go into a breeding. The best way to reduce the appearance of this gene within the breed is to follow these guidelines:
- When possible, breed Normal/Normal dogs – If only dogs free of the mutation were bred, the mutation would disappear. However, we have so many other considerations when breeding, it may not be in the best interest of the breed to only select Normal/Normal dogs.
- Breed Mutant/Normal dogs only to Normal/Normal dogs – When you breed a dog with one copy of the mutant gene, try to breed him to a Normal/Normal dog. This will prevent any of the offspring from being Mutant/Mutant , which is the most serious condition. In a breeding such as this, statistically 50% of the offspring will be Mutant/Normal and 50% will be Normal/Normal.
- Avoid breeding Mutant/Mutant dogs, but if that’s not possible, breed them only to Normal/Normal dogs – Mutant/Mutant dogs will always pass the mutant gene to their offspring. Ideally we would avoid breeding them, but again, with other considerations to breeding, this may not always be ideal. Breeding a Mutant/Mutant dog to Normal/Normal dog ensures that none of the offspring will be Mutant/Mutant. All the offspring of such a breeding will be Mutant/Normal.
If You Don’t Test
Testing your dogs for the mutant gene can be costly if you have multiple dogs. If you elect not to test your dogs, here are some things to consider:
- Even if your current heartworm prevention contains Ivermectin and your dogs have had no reaction, it does not mean they don’t carry the mutation. Normal levels of Ivermectin – the amount that appears in heartworm medicine – will often not cause a reaction in carriers. If your vet gives your dog a higher than normal dose – for example to treat heartworm or other parasites – this is when you might see an issue. It is also possible to not see a reaction to Ivermectin but to see a reaction to another drug.
- Every time your dog is given a new drug or a higher dosage of a drug, keep this issue in mind. If your dog should have a reaction, your vet may be able to treat it more effectively if you call this potential reason to his attention.
- Look in the databases: Look in the OFA and WS Genetics databases for relatives of your dog. This may give you information on your own dog. For example, if both parents of your dog are Normal/Normal, your dog will be Normal/Normal as well and you don’t need to test him.
Some of the potential problem drugs are used routinely, but some would only be used in serious situations. For example, if your dog needs to undergo chemotherapy, that would be their first exposure to the anti-cancer drugs in the list. The MDR1 mutation is a relatively simple issue, but unfortunately one that could become relevant when you least want it to. It’s better to be informed up front and file it away as another piece of information that could help you provide the best care for your dogs.
Additional Resources:
The VCPL Homepage on Multidrug Sensitivity
Study by UC Davis – The Genetics of Ivermectin Sensitivity in Breeds from the Working Collie Lineage
Buster Alert – the story of Buster from Mini Aussie Rescue & Support
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