Multidrug Resistance 1
Multidrug Resistance 1
Disease Name 2
Multi-Drug Resistance Gene, (MDR) codes for a protein that is responsible for protecting the brain by transporting potentially harmful chemicals away from the brain. In certain breeds, a mutation in the MDR1 gene causes sensitivity to Ivermectin, Loperamide, and a number of other drugs. As a result of the accumulation of toxins, the dog can show neurological symptoms including: ataxia, tremors, seizures, excessive salivation, obtundation, bradycardia, mydriasis, loss of menace, loss of papillary light responses, coma and respiratory arrest. Age of onset from birth, but symptoms only noted when exposed to drugs causing sensitivity.There are many different types of drugs that have been reported to cause problems. Some drugs include: Acepromazine, Butorphanol, Cyclosporin, Digoxin, Doxorubicin, Doramectin, Emodepside, Erythromycin, Ivermectin, Loperamide (Imodium), Milbemycin, Moxidectin, Paclitaxel, Rifampin, Selamectin, Vinblastine, Vincristine. Please note this list is not exhaustive and could be subject to change.
Multidrug resistance 1 is caused by a lack of P-glycoprotein drug transporter in the blood-brain barrier, which is characterized by neurotoxicity after administration of certain drugs. A genetic test is available. Neurotoxicity following drug administration, which varies according to dose, is the main sign. Dogs may show ataxia, tremors, seizures, excessive salivation, obtundation, bradycardia, mydriasis, loss of menace, loss of papillary light responses, coma and respiratory arrest (Mealey et al., 2001). P-gp normally transports some chemotherapeutic agents (Vinca alkaloids, doxorubicin), immunosuppressants (cyclosporine, tacrolimus), macrocyclic lactone antiparasitic drugs (ivermectin, loperamide, milbemycin, selamectin, moxidectin), HIV-1 protease inhibitors, and steroid hormones. (From OMIA)
Washington State University owns Patent on MDR1 genotyping: US 6790621. Wisdom Health is the only entity licensed to perform MDR1 genotyping in conjunction with breed analysis and genetic screening for multiple diseases and traits in the United States
Mealey, KL., Bentjen, SA., Gay, JM., Cantor, GH. : Ivermectin sensitivity in collies is associated with a deletion mutation of the mdr1 gene. Pharmacogenetics 11:727-33, 2001. Pubmed reference: 11692082.
Mizukami, K., Yabuki, A., Kohyama, M., Kushida, K., Rahman, M.M., Uddin, M.M., Sawa, M., Yamato, O. : Molecular prevalence of multiple genetic disorders in Border collies in Japan and recommendations for genetic counselling. Vet J 214:21-3, 2016. Pubmed reference: 27387721. DOI: 10.1016/j.tvjl.2016.05.004.
Donner J, Kaukonen M, Anderson H, Moller F, Kyostila K, Sankari S, Hytonen M, Giger U, Lohi H. Genetic Panel Screening of Nearly 100 Mutations Reveals New Insights into the Breed Distribution of Risk Variants for Canine Hereditary Disorders. PLoS One. 2016 Aug 15;11(8):e0161005. [PubMed: 27525650]
Gramer, I., Leidolf, R., Doring, B., Klintzsch, S., Kramer, EM., Yalcin, E., Petzinger, E., Geyer, J. : Breed distribution of the nt230(del4) MDR1 mutation in dogs. Vet J 189:67-71, 2011. Pubmed reference: 20655253. DOI: 10.1016/j.tvjl.2010.06.012.
Gene Name Text
ATP-binding cassette, sub-family B (MDR/TAP), member 1
The discovery of the MDR1 mutation in dogs, establishment of genotyping procedures, development of all reagents, and research into specific problem drugs was made or conducted by Washington State University.