Multi-Drug Resistance

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Find out if your dog could develop Multi-Drug Resistance at CAGT.

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In certain breeds a mutation on the ABCB1 gene, which encodes the MDR1 protein (which stands for Multi Drug Resistance 1) can cause animals that carry the mutation to be particularly sensitive to certain drugs. The variant was first detected in a subpopulation of dogs that were highly sensitive to Ivermectin-induced neurotoxicity. The variant on the ABCB1 gene results in the brain being unable to efficiently pump some drugs out, causing a toxic build-up of these drugs in the brain. Dogs subsequently experience and range of symptoms from vomiting and diarrhea to lethargy, seizures, or coma.

A whole range of drugs are pumped out of the brain by the MDR1 protein pump, including antiparasitics, immunosuppressants, antidiarrheals, chemotherapy, antibiotics, antihistamines and more. More details on the drugs that can be dangerous for dogs can be found here. Your vet should be aware if your dog has one or two copies of the defective ABCB1 gene, as it may affect future treatment options.

This genetic defect is known to occur in up to 75% of some dog breed populations, and is particularly common in Rough Collies, Smooth Collies, Shetland Sheepdogs, Australian Shepherds, Miniature Australian Shepherds, Silken Windhounds and White Swiss Shepherds.

Autosomal Dominant

The 4 bp deletion in the gene called ABCB1 that causes Multi-Drug Resistance in many breeds is autosomal dominant. This means that dogs that carry one or two copies of the mutation (heterozygotes and homozygotes respectively) may have adverse reactions to some drugs. They will also pass the mutation on to all (for homozygotes) or about half (for heterozygotes) of any offspring they have. Breeding dogs that will not develop Multi-Drug Resistance should be the breeder’s priority, with a reduction in mutation frequency within the whole breed being the secondary, longer-term target.

Due to the frequent occurrence of the mutation in many breeds, carriers can be bred from (to avoid excessive limitation on the breed gene pool), but they should be mated to a dog that has also been tested and is clear of the ABCB1 mutation (i.e. carry no copies of the mutation). If a carrier is mated to a clear dog approximately half of the resulting puppies will also be carriers and may develop Multi-Drug Resistance caused by the ABCB1 mutation. It is advisable to also DNA test all puppies of such matings to ensure that their future owners and veterinarians are aware of their status with regards to Multi-Drug Resistance.

Gene ABCB1
Variant 4 bp (AGAT) deletion (c.228_231del)
Assay Type Variant Specific
Inheritance Autosomal Dominant
Severity Low-Moderate: Affected animals experience discomfort or dysfunction of some kind, but life expectancy is not affected.

Alves L, V Hulsmeyer, A Jaggy et al. (2011) Polymorphisms in the ABCB1 gene in phenobarbital responsive and resistant idiopathic epileptic Border Collies. J Vet Intern Med. 25(3): 484-489 . DOI: 10.1111/j.1939-1676.2011.0718.x.

Barbet JL, T Snook, JM Gay et al. (2009) ABCB1-1 Delta (MDR1-1 Delta) genotype is associated with adverse reactions in dogs treated with milbemycin oxime for generalized demodicosis. Vet Dermatol. 20(2): 111-114 . DOI: 10.1111/j.1365-3164.2008.00725.x.

Donner J, M Kaukonen, H Anderson et al. (2016) Genetic Panel Screening of Nearly 100 Mutations Reveals New Insights into the Breed Distribution of Risk Variants for Canine Hereditary Disorders. PLOS ONE. 11(8): e0161005 . DOI: 10.1371/journal.pone.0161005.

Firdova Z, E Turnova, M Bielikova et al. (2016) The prevalence of ABCB1:c.227_230delATAG mutation in affected dog breeds from European countries. Res Vet Sci. 106(89-92 . DOI: 10.1016/j.rvsc.2016.03.016.

Geyer J, S Klintzsch, K Meerkamp et al. (2007) Detection of the nt230(del4) MDR1 mutation in White Swiss Shepherd dogs: case reports of doramectin toxicosis, breed predisposition, and microsatellite analysis. J Vet Pharmacol Ther. 30(5): 482-485 . DOI: 10.1111/j.1365-2885.2007.00885.x.

Gramer I, R Leidolf, B Doring et al. (2011) Breed distribution of the nt230(del4) MDR1 mutation in dogs. Vet J. 189(1): 67-71 . DOI: 10.1016/j.tvjl.2010.06.012.

Mealey KL, SA Bentjen, JM Gay et al. (2001) Ivermectin sensitivity in collies is associated with a deletion mutation of the mdr1 gene. Pharmacogenetics. 11(8): 727-733 . DOI: 10.1097/00008571-200111000-00012.

Mealey KL and KM Meurs et al. (2008) Breed distribution of the ABCB1-1Delta (multidrug sensitivity) polymorphism among dogs undergoing ABCB1 genotyping. J Am Vet Med Assoc. 233(6): 921-924 . DOI: 10.2460/javma.233.6.921.

Mizukami K, HS Chang, A Yabuki et al. (2012) 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. 24(1): 127-134 . DOI: 10.1177/1040638711425591.

Neff MW, KR Robertson, AK Wong et al. (2004) Breed distribution and history of canine mdr1-1Delta, a pharmacogenetic mutation that marks the emergence of breeds from the collie lineage. Proc Natl Acad Sci U S A. 101(32): 11725-11730 . DOI: 10.1073/pnas.0402374101.

Nelson OL, E Carsten, SA Bentjen et al. (2003) Ivermectin toxicity in an Australian Shepherd dog with the MDR1 mutation associated with ivermectin sensitivity in Collies. J Vet Intern Med. 17(3): 354-356 . DOI: .