Disease overview

Multidrug Resistance mutation refers to a specific mutation that can occur in the MDR1 gene, also known as the ABCB1 gene. This gene codes for p-glycoprotein, which helps clear chemicals and potential toxins from cells. A mutation in the MDR1 gene makes some dogs more sensitive to the adverse effects of certain medications, including sedatives, anti-parasitics (specifically ivermectin), gastroprotectants (e.g., antacids and anti-diarrhea medications), and anti-cancer medications. This is because the defective p-glycoproteins that result from the mutation allow higher levels of drugs to pass the blood-brain barrier and thus increase the neurological effects of these medications.

Gene name

ABCB1 (MDR1)

Inheritance

Autosomal dominant with incomplete penetrance

Signs and symptoms

Symptoms occur only after a dog receives either of the drugs that are known to cause problems in dogs carrying an MDR1 mutation. In other words, a dog with the MDR1 mutation will not exhibit symptoms simply because they have the mutation. Once an anti-parasitic, gastroprotectant, or anti-cancer drug has been administered, clinical signs include diarrhea, vomiting, and lethargy, as well as more serious symptoms such as seizures or coma. Therefore, genetic testing to find out if a dog has the MDR1 mutation before the possibility of having any of these drugs administered can help avoid such effects (i.e., alternative drugs or dosages can be explored).

How is it diagnosed

Genetic testing for the MDR1 mutation is the ideal proactive approach, so that use of MDR1 problem drugs can be avoided in high-risk breeds.

Breeds at higher risk

Herding breeds, most commonly and

Citations

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. doi: 10.1097/00008571-200111000-00012. PMID: 11692082.

Han JI, Son HW, Park SC, Na KJ. Novel insertion mutation of ABCB1 gene in an ivermectin-sensitive Border Collie. J Vet Sci. 2010 Dec;11(4):341-4. doi: 10.4142/jvs.2010.11.4.341. PMID: 21113104; PMCID: PMC2998746.

Neff MW, Robertson KR, Wong AK, Safra N, Broman KW, Slatkin M, Mealey KL, Pedersen NC. 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. 2004 Aug 10;101(32):11725-30. doi: 10.1073/pnas.0402374101. Epub 2004 Aug 2. PMID: 15289602; PMCID: PMC511012.

Barbet JL, Snook T, Gay JM, Mealey KL. ABCB1-1 Delta (MDR1-1 Delta) genotype is associated with adverse reactions in dogs treated with milbemycin oxime for generalized demodicosis. Vet Dermatol. 2009 Apr;20(2):111-4. doi: 10.1111/j.1365-3164.2008.00725.x. Epub 2008 Dec 18. PMID: 19171022.

Gramer I, Leidolf R, Döring B, Klintzsch S, Krämer EM, Yalcin E, Petzinger E, Geyer J. Breed distribution of the nt230(del4) MDR1 mutation in dogs. Vet J. 2011 Jul;189(1):67-71. doi: 10.1016/j.tvjl.2010.06.012. Epub 2010 Jul 23. PMID: 20655253.

https://vcpl.vetmed.wsu.edu/problem-drugs

Disclaimer

Disease diagnosis and treatment should always be performed by a veterinarian. The following information is for educational purposes only.