MDR1 Drug Sensitivity
What is MDR1?
MDR1 is the commonly used name for a genetic variant affecting the ABCB1 gene. This gene provides instructions for producing P-glycoprotein, which helps prevent certain medicines and toxins from accumulating within the brain.
Dogs with one or two copies of the MDR1 variant may be more sensitive to certain medicines. The greatest risk is generally found in dogs with two copies, although dogs with one copy can also experience adverse reactions.
The variant is found most often in herding breeds and some related breeds, including:
- Rough Collies
- Smooth Collies
- Shetland Sheepdogs
- Australian Shepherds
- Miniature American Shepherds
- Old English Sheepdogs
- Border Collies
- German Shepherd Dogs
- Longhaired Whippets
- Silken Windhounds
- Some cross-bred dogs with ancestry from affected breeds
Medicines associated with MDR1 sensitivity
Medicines known to require particular care can include certain:
- Antiparasitic medicines, including ivermectin and related drugs
- Antidiarrhoeal medicines, particularly loperamide, also known as Imodium
- Chemotherapy medicines, including vincristine, vinblastine and doxorubicin
- Sedatives and anaesthetic-related medicines
- Opioid medicines
- Other medicines transported by P-glycoprotein
The risk may depend on the particular medicine, dose, route of administration and the dog’s genotype. A medicine that is acceptable at one dose may be dangerous at a higher dose.
Check current MDR1 medicine information from Washington State University
Do not give loperamide, ivermectin or any other medicine to a Collie without veterinary advice. Never use medication intended for another animal or human.
Possible signs of an adverse reaction
Symptoms depend on the medicine and the amount given but may include:
- Excessive or prolonged sedation
- Weakness or loss of coordination
- Tremors
- Excessive salivation
- Dilated pupils
- Visual impairment or apparent blindness
- Vomiting
- Slow heart rate
- Seizures
- Collapse, coma or death in severe cases
MDR1 DNA testing
A DNA test can identify whether a dog has zero, one or two copies of the tested MDR1 variant. Testing normally uses a simple cheek swab or blood sample and can be carried out at any age.
MDR1 normal/normal
The dog has two normal copies of the tested gene and is not considered to have an increased risk of sensitivity caused by this MDR1 variant.
The dog will not pass this particular variant to its puppies.
MDR1 mutant/normal
The dog has one copy of the MDR1 variant and one normal copy. This is sometimes described as a carrier or heterozygous result.
Dogs with one copy can still be sensitive to certain medicines, although their reactions may be less severe or may occur at higher doses than in mutant/mutant dogs.
Each puppy has a 50% chance of inheriting the variant from this parent.
MDR1 mutant/mutant
The dog has two copies of the MDR1 variant and is at the greatest risk of severe or potentially fatal reactions to certain medicines.
The dog will pass one copy of the variant to every puppy.
Why “clear, carrier and affected” can be confusing
Some laboratories use the words clear, carrier and affected. Washington State University prefers the more precise descriptions:
- MDR1 normal/normal
- MDR1 mutant/normal
- MDR1 mutant/mutant
This avoids the mistaken belief that a dog with one copy cannot react to medication. Both mutant/normal and mutant/mutant dogs can have increased drug sensitivity.
Information provided by Dr Katrina Mealey, Washington State University:
The Veterinary Clinical Pharmacology Laboratory discovered the MDR1 mutation and generated much of the research on the subject.
The laboratory does not use simple plus and minus symbols because they can cause confusion. It uses the descriptions MDR1 mutant/mutant, MDR1 mutant/normal and MDR1 normal/normal.
Expected inheritance
The figures below are the expected probabilities for each puppy. Actual numbers within a small litter may differ by chance.
| First parent | Second parent | Expected puppies |
|---|---|---|
| Normal/normal | Normal/normal | 100% normal/normal |
| Normal/normal | Mutant/normal | 50% normal/normal and 50% mutant/normal |
| Normal/normal | Mutant/mutant | 100% mutant/normal |
| Mutant/normal | Mutant/normal | 25% normal/normal, 50% mutant/normal and 25% mutant/mutant |
| Mutant/normal | Mutant/mutant | 50% mutant/normal and 50% mutant/mutant |
| Mutant/mutant | Mutant/mutant | 100% mutant/mutant |
Breeding considerations
MDR1 results can be used to avoid producing puppies with two copies of the variant while retaining genetic diversity.
A mutant/normal dog can be mated to a normal/normal dog without producing mutant/mutant puppies. The expected puppies will be either normal/normal or mutant/normal.
A mutant/mutant dog mated to a normal/normal dog will produce mutant/normal puppies. These puppies may still have some increased drug sensitivity and their owners should be told their status.
Every puppy that may have inherited the variant should be tested before being used for breeding.
MDR1 and anaesthesia
Some sedatives, pain-relieving medicines and anaesthetic-related drugs may have stronger or more prolonged effects in dogs with an MDR1 variant.
This does not mean that an MDR1 dog cannot receive necessary surgery or anaesthesia. It means that the veterinary surgeon must know the dog’s breed and test result so that appropriate medicines, doses and monitoring can be selected.
Rough Collies and General Anaesthesia – PDF
Testing and further articles
Recording results
Results from laboratories participating in The Royal Kennel Club’s official DNA-testing schemes may be sent directly for recording when the required identification and owner consent have been provided.
Check with the testing laboratory before submitting a duplicate result. For current information about recording results, contact The Royal Kennel Club or email:
