In some breeds (e.g. Australian Shepherd, Collie), there is a genetic mutation that makes dogs sensitive to certain drugs, including anti-parasite treatments. It is advisable to test dogs of these breeds to see if they are carriers of this mutation. The MDR1 gene mutation mainly affects Collie dogs. It is also found in other herding dog breeds: Shetland Shepherd, Australian Shepherd, Border Collie, White Swiss Shepherd, etc...
MDR1 stands for Multi Drug Resistant: this gene is indeed essential for the elimination of certain molecules. If it is deficient, serious symptoms appear after ingesting certain drugs, even common ones, such as anti-parasitics or anti-diarrheal.
Let’s find out all about the MDR1 gene and how to protect your dog from it.
The MDR1 gene mutation
It is a mutation affecting the MDR1 gene, MDR standing for multi-molecule resistance. The MDR1 gene codes for a protein located at the level of the blood-meningeal barrier (barrier located in the brain and separating the bloodstream from the nervous system). When the MDR1 gene is mutated, this protein is non-functional or absent and certain drugs will accumulate in the nervous system.
In cells, the chromosomes are paired, so there are two MDR1 genes in an individual.
If a dog has both MDR1 genes mutated, then it is said to be homozygous recessive (-/-). These are the most drug-sensitive dogs and great care must be taken with the drugs used.
If a dog has a mutated gene, then it is heterozygous (+/-). Care must also be taken as they may show symptoms following medication but these are generally less severe than in homozygous mutants.
Finally, a dog that does not have a mutation is said to be homozygous dominant (+/+). Dogs without the mutation naturally tolerate "all" drugs.
So for example, if your Australian Shepherd has the MDR1 gene mutation on both chromosomes (homozygous recessive), he will have total drug sensitivity and a high risk of developing serious, even fatal side effects. If he has the mutation on only one chromosome (heterozygous), he will produce the protein but in a reduced quantity, his risk will be lower but not totally null.
How common is MDR1 in Australian Shepherds?
It is considered that about 50% of Australian Shepherds carry the genetic anomaly and are therefore at high or moderate risk of developing a drug sensitivity with certain products.
This genetic mutation does not only affect the Australian Shepherd; it also affects :
- The Collie
- The Shetland
- The White Swiss Shepherd
- Border Collie
- English Shepherd
- German Shepherd
- Old English Sheepdogs
Symptoms of drug intoxication
The symptoms are mainly neurological and, to a lesser extent, digestive. In the 48 hours following the absorption of the drug, the dog will present:
- Gait problems or even paralysis
- Fatigue, which may even lead to coma
- Dilated pupils or reduced vision
- Vomiting, diarrhoea or hypersalivation
In this case, you should go to your veterinarian or to an emergency centre urgently. There is no specific antidote for this poisoning, but treatments to eliminate the product and support the body will be implemented. Your dog will probably be hospitalised and given a drip.
It is important that you give the name of the drug your pet ingested, even if it was not prescribed by a vet. The symptoms may vary somewhat depending on the drug used.
What does it mean if a dog is an MDR1 carrier?
The administration of certain drugs, even at normal doses, leads to neurotoxicity in dogs with genetic drug sensitivity. Indeed, when the MDR1 (MultiDrug Resistance) gene is mutated, the corresponding protein (MDR1-PGP), whose function is to expel toxic molecules from the central nervous system, is inactive. It cannot therefore fulfil its neuroprotective function.
To make it simpler, there are medications that you won’t be able to give a dog who has the MDR1 gene. As is often the case, and even more so in this situation, prevention is better than cure.
What are the reasons you should test your dog?
For prevention: Your vet and yourself will be able to adapt your dog’s prescription with an alternative treatment, without danger for the animal's health. Indicate on the animal's health record its genetic status with regard to drug sensitivity. Don’t forget to inform people about the risks of the MDR1 gene and what to do in the event of intoxication.
To confirm a diagnosis: If a dog presents symptoms of neurological intoxication, you will get a confirmation of the diagnosis with an MDR1 test and will be able to let your veterinarian know about it. In case in the future your vet needs to operate on your dog, it would be very important information to know.
To advice on breeding: You advise your breeders to check their breeding stock in order to adapt the matings and avoid the birth of homozygous dominant puppies. To avoid degrading the genetic diversity within breeds, heterozygous dogs should not be excluded from reproduction.
MDR1 gene testing
You will have understood, it is important to know if your Australian Shepherd, Collie, Shetland or any other herding dog breeds are carrying a mutation on the MDR1 gene or not. To do this, nothing could be simpler than to carry out a genetic analysis. This examination (a mouth test) is painless and without risk for your pet.
Your vet will pass a small brush inside your dog’s cheek. The brush is then sent to a specialised laboratory to analyse the DNA of your pet.
A few days later, you will receive the results:
| MDR1 mutation | Risk of drug poisoning |
|---|---|
| Normal/Normal (+/+) | None |
| Normal/Mutant (+/-) | Moderate risk |
| Mutant/Mutant (-/-) | Very high risk |
The list of dangerous drugs for dogs carrying the MDR1 gene
If your dog is homozygous dominant for MDR1, and to a lesser extent heterozygous, certain drugs should be avoided. These are:
- Ivermectin, doramectin: antiparasitics rarely used on pets except in case of recalcitrant demodicosis
- Emodepside (Profender®): a dewormer
- Acepromazine (tranquiliser and pre-anesthetic agent)
- Loperamide (Imodium®, loperal®) against diarrhoea
- Selamectin, milbemycin, and moxidectin (antiparasitic agents)
- Butorphanol (analgesic and pre-anesthetic agent)
- Chemotherapy Agents (Vincristine, Vinblastine, Doxorubicin, Paclitaxel)
- Apomorphine: this drug is used to induce vomiting in dogs that have ingested poisons/toxins.
Some molecules should be avoided or used with caution (reduced dosage). These include:
- Anti-vomiting drugs (Domperidone (Motilium®))
- Antacids (Cimetidine (Zitac®), Ranitidine)
- Immunomodulators (Cyclosporin A (Atopica®), tacrolimus)
- Anti-cancer drugs (doxorubicin, vinblastine, vincristine)
- Anti-inflammatory or analgesic drugs (dexamethasone, butorphanol, morphine)
- Tranquillisers (acepromazine (Calmivet®))
- Heart medicines (Digoxin, quinidine, verapamil, diltiazem, etc.)
Be careful, this list is not exhaustive! In any case, it is advisable not to give your dog any medication without veterinary advice. Nor should you leave your medication lying around. Many dogs are gluttonous and ingesting human medication could be fatal in the case of a mutation of the MDR1 gene.
Translated version from an article written by veterinarian Isabelle Vixège.
