The product of MDR1 gene is a protein responsible for transport of different substances across cell membrane. It is found in membranes of intestinal epithelial cells, proximal kidney tubules and liver hepatocytes. The action of this protein is connected to removal of certain molecules out of an organism through urine and bile. The protein is also found on a blood-brain boundary and is responsible for restriction of entry of such molecules into central nervous system. The protein is able to carry a wide spectrum of structurally unrelated drugs, toxins and xenobiotics as well as certain drugs commonly used in veterinary diagnostics. A mutation in MDR1 gene causes the production of non-functional protein which in turn causes sensitivity on certain drugs, especially ivermectin.
Clinical signs in animals with MDR1 gene mutation are expressed after application of certain drugs. Substances that have been shown to cross blood-brain barrier and cause severe symptoms are: ivermectin, doramectin, moksidectin and loperamid. The use of these drugs is discouraged in dogs shown to have MDR1 mutation. Change in pharmacokinetics has also been shown for certain drugs and a strict veterinarian monitoring of an animal is advised. These drugs include: cytostatics, immunosuppressives, digoxin, methyldigoxin, opioids (morphine), antiaritmics, antiemetics, antihystaminics and glucocorticoids.
Inheritance: autosomal recessive- read more
Mutation: MDR1 (Mealey et. al., 2005)
Genetic test: Disease or carrier can be identified by genetic testing at any age. The RT-PCR method used for testing is extremely accurate and allows complete differentiation between affected animals, carriers and healthy dogs.
Disease control: read more
Affected breeds: Rough Collie, Smooth Collie, Border Collie, Shetland Sheepdog, Australian Shepherd, English Shepherd, McNab, Old English Sheepdog (Bobtail), Longhaired Whippet, Silken Windhound, White Shepherd, German Shepherd, Wäller
Sample: EDTA whole blood (1.0 ml) or buccal swabs. Detailed information about sampling can be found here.