Drug Sensitivity - MDR-1 GENE

For many months these mice lived an entirely normal existence, eating, sleeping, mating and rearing their young, researchers began to think the missing MDR1protein was making no difference at all to the lives of these mice, until the mice developed a mite infestation. The cages were sprayed with Ivermectin, the following day every mouse was dead.

Since this time we have discovered many drugs fatal to collies carrying the double MDR1 gene mutation (-/-).
For years I have kept a private data base of collies having died of liver and kidney problems, having experienced liver problems myself in the past, I wanted to know if other dogs dying with these problems were related to those I had lost myself. Over the years the data base grew and remained quite confusing, that is until we discovered the MDR1 problem. As people began to make public the MDR1 status of their dogs I began to notice a pattern emerging. The lines commonly found to contain a large number of (-/-) dogs, were in fact often the same lines from which the dogs in my data base were bred. More recently, some dogs have died after having been tested for the MDR1 mutation, to press these have all been -/- , food for thought!

Plus, when it was discovered a line free of liver problems, and included it into Wicani´s breeding programme, not only did she got her dogs  rid of liver problems, but when they were tested for MDR1, they were +/+ in other words they were free of the mutation. This could be coincidence, so Angela began research into what happens when the MDR1 protein is absent in humans.

It seemed common sense to her, that if poisons and chemicals were crossing the blood brain barrier and entering the brain, surely lesser toxins were doing this all the time but not to an immediately fatal degree.
As the MDR1 protein is responsible for pumping these toxins away from the brain and out of the system, could these toxins be remaining in the body and being stored in the liver? What about the toxins and chemicals normally passed through the dogs body from complete diets, travel sickness pills etc; were these being stored in body organs, building up over time to create problems? If I was correct with her theory, the result would be fabulous, it would mean the final solution is within our grasp to rid our breed of some of the persistent liver and kidney related problems that have plagued us.

Angela´s research into humans revealed some interesting facts, one being that when the MDR1 P-glycoprotein is absent, the placenta works differently. Poisons, lesser toxins and even some viruses not only cross the blood brain barrier; they also cross the placenta when they would not normally do so. Such humans often suffer with Colitis too. Ring any bells yet?

For a long time she wondered how research into this gene mutation in Collies could be funded, my prayers have been answered. Giessen University have now done several studies, the results are proving to be very interesting.

Steroids like Cortisol are also transported by the P-glycoprotein (this is the protein that cannot be produced by MDR1 -/- dogs) a new study has now been done in this area. One thing quickly became apparent, in MDR1 -/- dogs there is a lower level of Cortisol in the body, predisposing such dogs to greater problems when under stress. It would appear that MDR1 dogs really do suffer more stress and stress related illnesses.
Other revelations presented by Professor Dr. Geyer of the University are, the placenta works differently when the bitch is MDR1 -/- and yes, toxins, viruses and chemicals do cross the placental barrier in bitches and not only humans.
There are now at least 100 substances known to be dangerous to the MDR1 double mutant dog, and the list is growing.
The fact that such dogs have a huge improvement in health when fed a natural raw meat diet emphasizes the possible problems with toxin overload when fed a modern complete diet. In MDR1 -/- dogs, antibiotics are far more dangerous. Most people never consider antibiotics to be poisonous but they ARE they are designed to poison bacteria.

Certain antibiotics can destroy the liver of a double mutant dog within days..!!!! If your dog is in this category, and needs such medication, ask your vet to do blood tests at regular intervals throughout the treatment to ensure no irreversible damage is being done. Antibiotics or steroids should NOT continue more than one week, and if they must, blood tests must also be done.
Many breeders presently have a policy of giving antibiotics randomly to bitches when mated, in light of this latest research is this really wise? Could this be one of the reasons some bitches are dying of liver failure shortly after whelping and could it responsible for ever decreasing litter sizes? Unless you know the status of your bitch, you could be poisoning her and possibly her puppies too!

MDR1 protein begins working when food or medicines enter the stomach. Many things are transported out when the dog is MDR1 +/+, but when the dog is MDR1 -/- the entire dosage enters the blood stream, where it is transported not only directly to the brain, but to every other organ of the body. They enter organ cells and the placenta of developing embryo where they remain for far too long.

Another big problem revealed itself. If an MDR1 -/- dog is given a cocktail of anesthesia AND antibiotics together, it can totally destroy the liver! When a bitch is spayed, such procedure is normal, how many collie bitches have died or been diagnosed with liver failure within a short time of being spayed?

In the past we knew nothing about the MDR1 P-glycoprotein, but now we do. In her opinion it is the single most important problem within our breed, but the good news is WE CAN BREED IT OUT. Unlike CEA (in the UK we presently have no known genetically clear eyed collies) and Hip Dysplasia (which I believe is polygenetic and influenced by environmental factors as well as genetic), MDR1 can be eradicated easily, and if we love the Breed, we owe it this much. Can we really continue breeding animals knowing they are or could be failing in this respect?

Perhaps we could begin by testing our dogs, and making those results known to all fellow breeders. Perhaps if our stud dog is -/- we should refuse bitches to him unless they are +/+ Likewise if your bitch is -/-, wouldn´t it be wise to find her a partner who is +/+?

Perhaps the next time you have a litter of puppies born and are debating which to keep because you particularly like two bitches, have them MDR1 checked and let the result decide. Slowly we can move forward.

Angela owned her first show collie in 1974; She began studying the breed in 1972. Rough collies have brought so much joy into her life. We live in exciting times; we live in a time when we can give something back to the breed. In her opinion the missing MDR-1 P-glycoprotein is the silent killer, being aware of every dogs status is one step closer to life.

The following links are recommended.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1636591

http://www.pubmedcentral.nih.gov/articlerender.fcgiartid=1636591&rendertype=table&id=t1-cvj47pg1165

http://www.vetmed.wsu.edu/depts-VCPL/genetics.aspx

http://www.vetmed.uni-giessen.de/pharmtox/juniorprof/research.php#res_02

http://www.scielo.br/scielo.php?pid=S0103-84782006000100056&script=sci_arttext


Contribuition:

Angela Harvey. (Wicani Collies) and Killochan Castle where I found this excellent summery about MDR-1 problems.

Thank you to both of you to help all of us to STEP into the right way of FUTURE!!!