Multi-drug Resistance (MDR1)

 

Gene: ABCB1

Transmission: Autosomal dominant, variable penetrance

Mutation: Deletion, ABCB1gene; c.259_262 del.4bp, p.(D77A fs STOP 16), exon4

Medical system: Pharmacogenetics

Breeds: Alaskan Malamute, American Foxhound, American Staffordshire Terrier/Amstaff, Australian Cattle Dog, Australian Shepherd, Basset Hound, Beagle, Berger Picard, Border Collie, Boxer, Chihuahua, Chinook, Chow Chow, Collie, Collie - Rough, Collie - Smooth, Doberman Pinscher, English Bulldog, English Shepherd, German Shepherd, Golden Retriever, Great Pyrenees, Koolie, Labrador Retriever, Lacy Dog, Lhasa Apso, Long-Haired Whippet, McNab Shepherd, Miniature American Shepherd, Miniature Australian Shepherd, Norwegian Elkhound, Old English Sheepdog, Pembroke Welsh Corgi, Poodle - Miniature (Dwarf), Rottweiler, Ryukyu Inu, Schnauzer - Miniature, Shetland Sheepdog, Shih Tzu, Shiloh Shepherd, Siberian Husky, Silken Windhound, Toy Australian Shepherd, Waller, White Swiss Shepherd, Yorkshire Terrier

Age of onset of symptoms: The animal is at risk from birth.

Multi-drug resistance (MDR1) is a genetic condition wherein dogs that carry mutations in the ABCB1 gene (also called MDR1 gene) are hyper-sensitive to commonly used veterinary drugs; for this reason, it is considered a pharmacologic genetic disease.  The MDR1 gene codes for a transporter protein that protects the brain from toxic small molecules by binding and transporting the molecules out of the brain.  A dog with two copies of the MDR1 gene mutated is particularly sensitive to toxicity from a range of drugs, including antiparasitic drugs (macrocyclic lactones such as Ivermectin), antibiotics (such as Erythromycin), tranquilizers (such as Acepromazine), antidiarrheal drugs (such as Loperamide), opioids (such as Butorphanol), and cancer chemotherapy drugs (such as Vincristine, Vinblastine, Doxorubicin).  Signs of toxicity can include loss of alertness, excessive salivation, pupil dilation, tremors, ataxia, seizures, slowed heart rate, coma, respiratory arrest and death. Note that signs of toxicity are much more severe for the animal that is double mutant but have been recorded for animals that carry a single mutation.  For this reason, the heredity of Multi Drug Resistance is classified as dominant with variable penetration, and although the double mutant animal is most at risk, care should still be taken when giving medication to carrier animals.

 

References:

Labgenvet blog

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

Link OMIA: [1402-9615]

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