Multidrug sensitivity in dogs with MDR1 gene mutation

A drug transport system exists on the outer membrane of cells that helps pump certain drugs orMultidrug sensitivity in dogs with MDR1 gene mutation toxins out of the cell.  The pump is a protein, called P-glycoprotein, which is encoded by a gene called the MDR1 gene (also called the ABCB1 gene).  The P-glycoprotein pump plays and important role in limiting the absorption of many types of drugs inside the cell and also serves a role in the normal excretion of drugs.  Areas of the body where the pump is particularly important include the blood-brain barrier, the blood-testes barrier, and the placenta.  It is also important in normal excretory functions of intestinal cells, the kidney, and the biliary system of the liver.  Some dogs, especially herding breeds of dogs, have a mutation of the gene that results in the production of a defective P-glycoprotein protein pump.  Dogs with the MDR1 mutated gene are not able to limit the absorption of certain types of drugs inside the cell leading to increased amounts of the drug inside the cell.  This can have dramatic effects on the animal, particularly when it involves brain cells.

Breeds of dogs affected by MDR1 gene mutation

Collies are the most commonly affected breeds of dog that carry the MDR1 gene mutation.  Approximately 3 out of every 4 Collies in the United States have the mutant MDR1 gene.  It has also been found in high frequency (approximately 50%) of the following breeds of dogs: Australian Shepherds and Long-haired Whippets.  The mutant MDR1 gene has been found to a lesser extent in the following breeds of dogs in decreasing order of frequency: Silken Windhounds, McNab Sheepdog, Shetland Sheepdogs (Shelties), English Shepherds, German Shepherds, Herding Breed Cross, Old English Sheepdogs, Mixed Breed Dogs, and Border Collies.

Dogs get a set of genes from both parents.  As a result, dogs with the mutated MDR1 gene can be either homozygous (mutant/mutant) or heterozygous (mutant/normal) for the mutated MDR1 gene.  A dog that is homozygous for the mutated MDR1 gene because it obtain a mutated form of the gene from both parents will be more susceptible to certain drugs than a dog that is heterozygous for the MDR1 gene mutation and only received a mutated form of the gene from one parent.  The only way to determine if an individual dog has the mutant MDR1 gene is to have the dog tested.

Testing for the MDR1 gene mutation

To test a dog for the MDR1 gene mutation, DNA is obtained from either blood or cheek cells using a brush.  Tests are performed at Washington State University’s College of Veterinary Medicine’s Clinical Pharmacology Lab.  Tests run on blood have to be submitted by a veterinary hospital. Owners can submit samples themselves by obtaining their dog’s cheek cells using a brush.  Test kits can be ordered online that provide the brush and instructions for how to collect a cheek swab DNA sample.  This website also provides information on the cost of the test.

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Dr Stephen Atwater

Stephen W. Atwater, DVM, MS, Diplomate ACVIM (oncology) is a board-certified veterinary oncology specialist. His professional interests include utilizing emerging therapies for difficult to treat cancers.

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