MDR1
You can find all information regarding MDR1 at: http://www.mdr1-defekt.de/index.php?lang=FR
The reason for the sensitivity of some animals to some drugs is the disorder in the gene function. The inheritance is recessive. In the normal healthy dog, the brain tissue and central nervous system are protected against high concentrations of drugs circulating in the vascular system. The "Multidrug Resistance gene 1" (the MDR1 gene) plays an important role in the barrier between blood capillaries and brain tissue. It encodes a large transmembrane protein, P-glycoprotein, which is an integral part of the blood-brain barrier. P-glycoprotein functions in a protective capacity to transport a variety of drug substrates, including Ivermectin, from brain tissue back into capillaries.
The phenomenon of "Ivermectin toxicity in Collies" was first described in 1983. Ivermectin (an antiparasitic agent) causes neurologic toxicity in some, but not all Collies, at doses that are 1/200th of the dose required to cause toxicity in other dogs. Neurologic manifestations of Ivermectin in susceptible dogs include hypersalivation, ataxia, blindness, coma, respiratory compromise, and death.
Dogs suffering from oversensitivity for Ivermectine have been documented to be susceptible to neurotoxicity induced by many other drugs as well.
Oversensitivity for certain drugs was first found in Collies, originally the disorder was called "Ivermectine oversensitivity" or "Ivermectine toxicity". Over the years it became clear that Ivermectine is just one of the drugs causing problems for the animals suffering from oversensitivity and that it is not only the Collie that suffers from this genetic disorder.
Dr. Mark Neff and his co-workers showed that the mutant allele mdr1-1Δ originates from an animal in the working sheepdog populations in Great Britain before the isolation of breeds by registry, so before ca. 1873. From there on the mutant allele was passed on to many modern Collie-breeds today and probably to other breeds as well.
Approximately three of every four Collies in the United States have at least one mutant mdr1-1Δ allele. The frequency is about the same in France and Australia, so it is likely that most Collies worldwide have the mutation. The MDR1 mutation has not only been found in Collies and related breeds like Shetland Sheepdogs (Shelties), Border Collies, Bearded Collies, Australian Shepherds, Australian Cattledogs and Old English Sheepdogs, but also in German Shepherds, White Swiss Shepherds, Long-haired Whippets, Silken Windhounds and a variety of mixed-breed dogs.
In general, we should be aware that in the past, when breeds were developed, often breeding stock of other populations (breeds) was used to improve certain characteristics. In the process of introducing the desired qualities (genes) into a breed, it cannot be avoided that many neutral as well as undesirable genes cross the barrier between breeds.
For the time being, in all cases where similar clinical symptoms of oversensitivity for drugs are found in breeds with "family ties" with the original British working sheepdogs or their descendants, checking with the MDR1 test would be advisable. If it can be proven that the defective allele mdr1-1Δ is present, applying that DNA test will help the breeders in their selection against the disorder. Even more important, it will help the owners of pet dogs in avoiding the negative effects of wrong medication in animals suffering from this devastating genetic disorder.
The MDR1 genotype of every individual dog is a combination of father’s (+ or -) and mother‘s (+ or -) genetic information. The only individuals who are deffected are the ones who inherit the predisposition from both parents. They are identified as -/- and they transmit the predisposition for the defect to all of their offsprings. The individuals with +/- are clinically healthy, but they can transmit the defect to their offsprings. The dogs with a normal genotype are identified as +/+ and none of their offsprings will be affected with MDR1 defect.
Diagnosis of the defect
All other contact and information regarding MDR1 can be found at
http://www.vetmed.uni-giessen.de/pharmtox/mdr1_defekt.html
http://www.vetmed.uni-giessen.de/pharmtox/mdr1_defekt/diagnostik.html (this is the contact for getting your dog diagnosed)
http://www.vetmed.wsu.edu/depts%2DVCPL/