Multi-Drug Resistance Gene 1
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Breeds: Alaskan Noble Companion Dog, Anatolian Shepherd, Aussiedoodle, Australian Cattle Dog, Australian Labradoodle, Australian Mix, Australian Mountain Doodle, Australian Shepherd, Australian Shepherd/Border Collie, Australian Stumpy Tail Cattle Dog, Bearded Collie, Beauceron, Belgian Malinois, Belgian Sheepdog, Belgian Shepherd, Berger Blanc Suisse, Border Collie, Bordoodle, Boxer, Central Asian Shepherd, Collie, English Shepherd, English Springer Spaniel, German Shepherd Dog, Long Haired Whippet, Miniature American Shepherd, Miniature Australian Shepherd, Mixed Breed, Mixed Breed (Dog), Nova Scotia Duck Tolling Retriever, Old English Sheepdog, Polish Lowland Sheepdog, Rough Collie, Scotch Collie, Scottish Collie, Sheepadoodle, Shetland Sheepdog, Shiloh Shepherd, Silken Windhound, Smooth Collie, Standard Poodle, Swiss White Shepherd, Toy Australian Shepherd, Unspecified, Unspecified Breed, Welsh Sheepdog, Whippet, White Shepherd, Working Sheepdog, Yorkiepoo
Description
The Multi-Drug Resistance Gene (MDR) is a gene that codes DNA for a protein that is responsible for protecting the brain by transporting potentially harmful chemicals away. In certain breeds, a mutation that occurs in the MDR1 gene causes sensitivity to a number of other common drugs. The protein mistakenly perceives these drugs as safe and never removes the drug. If dogs with MDR1 mutations are given these common drugs, the effects can prove deadly.
Dogs with this mutation have a defect in the P-glycoprotein that is normally responsible for transporting certain drugs out of the brain. The defective protein inhibits the dog's ability to remove certain drugs from the brain, leading to a buildup of these toxins. As a result, the accumulation of toxins leads to neurological symptoms such as seizures, ataxia, or even death.
Dogs that are homozygous for the MDR1 gene (meaning that they have two copies of the mutated gene) will always display sensitivity to Ivermectin and other similar drugs. These dogs will also always pass one copy of the mutation to all potential offspring.
Dogs that are heterozygous (meaning they have only one copy of the mutation) can still react to these drugs at higher doses. There is a 50% chance that a dog with one copy of the mutation will pass it on to any offspring. When breeding carriers together, it is important to realize that there is a 25% chance per puppy that they will be homozygous for the MDR1 gene and develop deadly “allergies” to the drugs listed below.
There are many different types of drugs that have been reported to cause problems. The following is a list of just some of the drugs:
- Ivermectin (found in heartworm medications)
- Loperamide
- (Imodium, an over-the-counter antidiarrheal agent)
- Anti-cancerous agents:
- Doxorubicin
- Vincristine
- Vinblastine
- Cyclosporin (immunosuppressive agent)
- Digoxin (heart drug)
- Acepromazine (tranquilizer)
- Butorphanol ("Bute" pain control)
The following drugs may also cause problems:
- Ondansetron
- Domperidone
- Paclitaxel
- Mitoxantrone
- Etoposide
- Rifampicin
- Quinidine
- Morphine
Possible Results
| Genotype | Description |
|---|---|
| M/M | At Risk: Dog has two copies of the MDR1 mutation and will experience sensitivity to ivermectin or other associated drugs. The gene will be passed on to every offspring. |
| n/M | At Risk: Dog has one copy of the MDR1 mutation and may experience sensitivity to ivermectin or other associated drugs at higher doses. |
| n/n | Clear: Dog is negative for the mutation associated with MDR1. |
Reference
Mealey KL, Bentjen SA, Gay JM, Cantor GH. Ivermectin sensitivity in collies is associated with a deletion mutation of the mdr1 gene. Pharmacogenetics. 2001 Nov; 11(8):727-33. [PubMed: 11692082]
Mealey KL, Meurs KM. Breed distribution of the ABCB1-1delta (multidrug sensitivity) polymorphism among dogs undergoing ABCB1 genotyping. J Am Vet Med Assoc. 2008 Sep 15;233(6):921-4. [PubMed: 18795852]
Mizukami K, Chang H, Yabuki A, Kawamichi T, Hossain MA, Rahman MM, Uddin MM, Yamato O. Rapid genotyping assays for the 4-base pair deletion of canine MDR1/ABCB1 gene and low frequency of the mutant allele in border collie dogs. J Vet Diagn Invest. 2012 Jan;24(1):127-34. [PubMed: 22362942]