Multidrug Resistance 1 (MDR1)
MDR1 is an inherited condition that makes affected dogs particularly sensitive to drugs like ivermectin (anti-parasitic) and loperamide (opioid to treat diarrhoea). In normal dogs the blood/brain barrier protects the brain cells from various drugs and toxins.
The MDR1 listed drugs, while valuable for veterinary care, are not a part of nature and can readily be avoided when you know a dog's MDR1 status. Breeders should consider the mutation to be a fault, but not a disqualifying one. Dogs with the mutation would best be bred to those that are Normal/Normal.
MDR1 is an autosomal dominant genetic disorder, which means that only one copy of the gene is necessary for the dog to be affected. There is therefore no such thing as an MDR1 carrier.
The MDR1 gene mutation is hereditary and is passed from parents to offspring. Each dog inherits 2 copies of the MDR1 gene—1 copy from each parent. Animals that inherit 2 abnormal copies (homozygous) will produce no normal p-glycoprotein and will be most strongly affected.
MDR1 can cause some serious drug toxicity side effects in a patient who is treated without knowledge of the gene's presence. Common side effects of drug toxicity in dogs with MDR1 include vomiting, weakness, lack of coordination, lethargy, tremors, seizures, blindness, and death.
A carrier, as related to genetics, is an individual who “carries” and can pass on to its offspring a genomic variant (allele) associated with a disease (or trait) that is inherited in an autosomal recessive or sex-linked manner, and who does not show symptoms of that disease (or features of that trait).
The manufacturer of Nexgard has tested the product for safety in dogs with the MDR1 mutation. No adverse effects were observed. Dogs with the MDR1 mutation are not at increased risk for adverse effects.
Research has shown the mutation occurs more frequently in certain breeds. Approximately three of every four collies in the United States have the mutant MDR1 gene. The frequency is about the same in France and Australia, so it is likely that most collies worldwide have the mutation.
Australian Shepherds have a slightly lower incidence, with 50% being affected to some degree. Mixed breed dogs of herding descent have a 35% chance of carrying one or more mutated copies of the gene, while only 10% of Shelties are affected.
Breeding advice: If your dog is a carrier or affected
Your dog should not be bred from. Mating this dog could produce affected puppies. Producing affected puppies could have a serious impact on their health and welfare.
Only $75 with results in 7 business days. The Multidrug Resistance 1 MDR1 Test is a fast and effective way of determining whether or not your dog has the mutated Multidrug Resistance MDR1 gene, also known as the ABCB1 gene, or is likely to pass it on to any offspring.
Genetic testing for MDR1 is recommended to identify dogs at risk for multidrug sensitivity. Affected dogs will only exhibit signs of neurotoxicity if exposed to certain drugs. Test results should be shared with the dog's veterinarian prior to pharmacological treatments.
Loperamide (ImodiumTM; antidiarrheal agent). At doses used to treat diarrhea, this drug will cause neurological toxicity in dogs with the MDR1 mutation. This drug should be avoided in all dogs with the MDR1 mutation. Selamectin, milbemycin, and moxidectin (antaparasitic agents).
A Pesticide That Targets the Central Nervous System
Isoxazolines are neurotoxic to more than just insects; they also affect mammals. There is a reason why so many dogs experience seizures, ataxia, and tremors after taking NexGard — the pesticide compromises the dog's central nervous system.
What if a dog consumes multiple NexGard or NexGard SPECTRA chewables? Safety studies have demonstrated that NexGard and NexGard SPECTRA have a wide safety margin, however, if your dog consumes multiple NexGard or NexGard SPECTRA chewables, please contact your veterinarian.
A safe anesthetic protocol for dogs with the mutation of MDR1 consists in a 50% reduction of the normal dose with the drugs involved, specially morphine, butorphanol, buprenorphine and acepromazine.
In other words, being a carrier does not mean that the person presents with a disease, but it does mean that there is a risk of passing on that disease to your offspring.
Pathogenic bacteria and infectious particles cause disease. Vectors and carriers are involved in disease transmission. A carrier is a person who has the disease but not the symptoms and is capable of passing it on to another person.
People are sometimes concerned or surprised about finding out that they carry a genetic condition. Every person on earth carries several genetic conditions (mutations), usually without any symptoms or signs, so it's actually quite normal to test positive.
MDR1 results from a mutation in the multi-drug resistance gene. This gene encodes a glycoprotein that is responsible for pumping many drugs and other toxins out of the brain. Dogs with the mutant gene cannot pump certain drugs out of the brain as a normal dog would, which may result in abnormal neurologic signs.
When considering the use of macrocyclic lactones such as ivermectin or moxidectin in dogs, veterinarians have followed the adage, “white feet, don't treat.” This refers to the known sensitivity of Scotch collies (both rough and smooth) to neurotoxicity when administered these drugs at higher than label doses.
MDR1 appears to be especially important in protecting the brain. In the gut, where MDR1 pumps from the enterocyte towards the lumen, MDR1 limits the uptake of hydrophobic drugs. In analogy, MDR1 may protect the hepatocyte against hydrophobic toxic drugs by transporting them into the bile.