It is now widely accepted that the Collie breeds (Rough Collies, Smooth Collies, and Border Collies) appear to be hypersensitive to certain toxins (natural or drug-induced) and are more prone to stress-related problems.
The problem first came to light in 1983 when several Collies died from Ivermectin poisoning and, since then, the veterinary profession has accepted this drug should never be given to Collies. More recently a Rough Collie died from eating horse faeces (Ivermectin is used for worming horses and any excess drug passes out with their faeces).
Researchers have since found that approximately 60% of Rough and Smooth Collies appear to be susceptible not only to Ivermectin, but to a wide range of other drug substances. The MDR1 (multi-drug resistant) gene is responsible for ensuring the the body's natural P-glycoprotein functions normally by protecting the body from both environmental toxins and adminstered toxins eg drugs, and acting as a transport mechanism moving substances from cell to cell. P-glycoproteins are normally extensively distributed in the blood-brain and blood-testes barriers as well as major organs such as the liver, kidneys, intestines and placenta. When they are present in the intestinal tract three things normally occur - the substance may be metabolised; it may enter the circulatory system; or it may be passed out of the large intestine with the faeces.
In MDR1-affected dogs the function of the P-glycoprotein is compromised so toxins may leak into the major organs. If these compounds leak across the blood-brain barrier, they enter the central nervous system causing toxic reactions such as excessive salivation, Ataxia, blindness, coma, respiratory problems or even death.
Because of the lack of the P-glycoprotein transporter in the body, an MDR1-affected dog also tends to have a deficiency of Cortisol (a steroid hormone produced by the Adrenal glands). Cortisol is responsible for stress management and the maintenance of an efficient immune system, and a deficiency can therefore lead to stress-related problems such as colitis or inflammatory bowel disease.
An MDR1 Normal dog (+/+) receives a healthy MDR1 gene from each of its parents and can therefore only pass on healthy genes to its offspring. Such animals do not exhibit drug toxicity.
A ‘Carrier' (+/-) is a dog that has received a normal MDR1 gene from one of its parents, and a defective gene from the other parent. Please bear in mind that a carrier can pass either a normal or a defective gene onto its offspring resulting in approximately 50% of the puppies inheriting a defective MDR1 gene. Unfortunately the dominance of the MDR1 + gene has been found to be incomplete as some ‘carrier' animals also appear to be susceptible to high doses of those drugs that cause problems in MDR1-affected dogs, that is, those with two defective MDR1 genes (-/-).
An Affected dog (-/-) receives a defective MDR1 gene from both its parents, so such dogs will display toxic reactions to a wide range of drug compounds (see list below). A genetic test for MDR1 was introduced in 2007 and it is most important that responsible breeders test their stock and use only Normal (+/+) dogs in their breeding programmes so as to eliminate the defective MDR1 genes as soon as possible.
If you have an MDR1-affected Collie (-/-) you could be in a position to save its life by providing your veterinary surgeon with a copy of its MDR1 Certificate and the list of drug compounds that your Collie should never be given. Of those vets who have already been asked to put MDR1 test results onto a Collie's records, all have been aware of the Ivermectin problem but have had no idea about the broad spectrum of drug compounds that can severely threaten an MDR1-affected dog. Please note there are usually alternative, safe drugs your Collie could be given instead.
The table here shows three classes of drug compounds: Class A includes substances that have been proven to pass through the blood-brain barrier in MDR1-affected dogs and cause problems; Class B lists substances which have shown interactions in animal tests, whereas Class C substances can be given without problems, even to affected dogs: