MDR 1 Gene Defect/Ivermectin Sensitivity in Collies and other breeds.
New information and info on results - as at 2 October on work being done at Bristol University. At the University
of Bristol we are currently investigating the prevalence of a defective
gene, known as the MDR-1 gene, in the dog population of the United Kingdom.
The MDR-1 mutation is a genetic defect which alters the sensitivity of
affected dogs to many different drugs commonly used by vets in this country.
This genetic mutation was found by chance in rough collies and is the
reason they are incredibly sensitive to a wormer called ivermectin, which
we now no longer recommend in this breed. However the genetic defect also
affects the way a great many other common drugs work (e.g. sedatives,
chemotherapy agents and cardiac drugs). Dogs which have the genetic mutation
are completely normal (and lead completely healthy lives) until treated
with a drug they are sensitive too. Usually these effects are mild and
resolve quickly. However sometimes they are more serious. Further information
on the MDR-1 mutation is enclosed. The MDR-1 mutation has recently been
found in dogs in the United States, Germany and Australia, but the number
of dogs affected within the United Kingdom is currently unknown. Obviously
knowing and understanding which breeds are affected and how likely a dog
within each breed is to have the mutation will help us treat many dogs
more effectively and hopefully reduce unnecessary side effects as a result
of this genetic defect. |
|
Update 22nd July 2007 Multi-drug resistance (MDR1) in Rough and Smooth Collies
Kate Mealey and Mark Neff’s research into the multi-drug sensitivity of certain breeds was made public in 2004 (School of Veterinary Medicine, University of California, Davis) and, since then, similar research has been ongoing in Germany, Switzerland and Australia. Since my ‘Ivermectin Revisited’ article (International Collie Society Handbook 2004) it appears that the list of drugs, then thought to give toxic reactions to certain dogs, has significantly increased. Several countries are now offering DNA tests for MDR1 in Rough and Smooth Collies, including the UK, and so I thought it time to update the current facts. Researchers have found that certain breeds of dog, mainly Collie breeds (Rough Collies, Smooth Collies, and Border Collies), Australian Shepherds, Long-haired Whippets, McNabs, Old English Sheepdogs, Shetland Sheepdogs, Silken Windhounds and white German Shepherd dogs, may inherit a defective or mutant MDR1 gene. The MDR1 gene is responsible for enabling the body’s P-glycoprotein to function normally. P-glycoprotein is a large protein that functions as a trans-membrane pump, transporting certain drug compounds from outside a cell to inside a cell. P-glycoproteins are normally found in the blood-brain barrier but also express themselves in the intestinal surface, liver, kidneys, placenta and testes. In the normal dog P-glycoprotein is responsible for transporting certain drug compounds, known as P-glycoprotein substrates, and when a substrate drug is present in the intestinal tract three things normally happen – the drug may be metabolised; enter the systemic circulation; or be passed out of the large intestine with the faeces. In affected dogs, the function of the P-glycoprotein is compromised and drug compounds may leak into the major organs. If these compounds leak across the blood-brain barrier, they enter the central nervous system causing toxic effects. The MDR1 gene defect is inherited as an autosomal recessive condition. An affected dog is homozygous for the mutant gene (MDR1/MDR1 or -/-), having received a defective MDR1 gene from each of its parents. Such animals will display toxic reactions to a wide range of drugs, as excessive amounts are absorbed through the blood-brain barrier into their brains. For instance, in cases of Ivermectin poisoning affected dogs exhibit excessive salivation, ataxia, blindness, coma, respiratory problems, and even death. A ‘carrier’ is heterozygous for the condition and classified as N/MDR1(+/-). Its test result states: “The analysed dog is a carrier of the mutation, in the MDR1-gene that has been shown to cause hypersensitivity towards certain drugs such as Ivermectin. The dog will not develop Ivermectin hypersensitivity caused by this mutation, but will pass the defect gene onto its offspring with a probability of 50%.” It is therefore important to note that, as well as passing on a normal MDR1 gene to its offspring, carriers can also pass on the gene mutation, therefore it is most important to detect carriers before they are used for breeding. MDR1 normal dogs (N/N or +/+) are homozygous for the healthy gene, and can only pass on the healthy gene to their offspring. Such animals do not exhibit drug toxicity. Since the Mealy/Neff research, the components of several other drugs (thought to be safe a few years ago) have since been found to cause toxicity to MDR1 affected (-/-) dogs. The table below shows those drug compounds that are currently known to cause problems in affected Collies:
If we know there are specific health issues with our Roughs and Smooth Collies, we surely owe it to them to try and eliminate or reduce the problem, by using the various tests that have been made available to us. If you find your Collie is affected with the defect MDR1 genes, you could be in a position to save its life by informing your veterinary surgeon and providing him/her with a list of drugs that could be life-threatening to your dog. At one time vets followed the theory of ‘white feet, don’t treat’, but now that more information is known the practice is ‘white feet, test to see if you can treat!’ The Laboklin Laboratories of Manchester (UK branch of the Laboklin Company of Bad Kissingen in Germany) now offer a simple DNA test for MDR1, using a buccal swab. This identifies normal, affected and carrier animals. The cost is currently £35.00 per dog, which will hopefully be reduced in the coming months. Collies can be tested at any age. Normal
dog - N/N or +/+
ps contact details To obtain your free swabs please contact Mansour Makki, Laboklin Laboratories (UK), 61 Mouldsworth Avenue, Manchester M20 1GG, tel. 01612 823066, email: m.makki@btinternet.com |
| Received
from Genetic diseases are avoidable conditions that cause sufferings to both dogs and their breeders. We offer
DNA test for the MDR1 Gene Defect/Ivermectin Sensitivity in Collies
and other breeds. Vets prescribe Ivermectin based drugs extensively for the prevention and treatment of parasite infections. Ivermectin is probably the most effective anti-parasite medication ever used. Some dogs exhibit adverse reaction to normal doses of Ivermectin drug and show neurotoxic symptoms ranging from tremors, anorexia and excess salivation to blindness, coma and death. These dogs display toxicity signs even at 1/200th of the dose required to cause toxicity in healthy dogs. These dogs are not only sensitive to Ivermectin but to other drugs as well [see list below]. Scientists discovered that these dogs lack a protein called P-Glycoprotein, which is responsible for limiting the penetration of many drugs and toxins into the brain, and that affected dogs show signs of toxicity because they are unable to stop drugs from permeating their brains. Researchers have identified that this condition is due to a mutation in the multi-drug resistance gene [MDR1] that prematurely prevents the formulation of P-Glycoprotein. The MDR1 mutation is inherited as a recessive condition, therefore a dog can have one or three conditions: healthy clear, healthy carrier of affected. Healthy clear dogs don't carry the mutation and therefore can safely be mated to other dogs. Healthy carriers carry the mutation and therefore can safely be mated to other dogs. Healthy carriers carry the mutation but since it is a recessive trait, they will not show signs of sensitivity, however, they may pass the mutation to their offspring. Affected animals carry a pair of the mutation and will pass it on to all their offspring. Approximately 35% of collies appear to be infected with this condition. the MDR1 mutation has also been found in Shetland Sheepdogs, Australian Shepherds, Old English Sheepdogs, German Shepherds, Long haired Whippets, Silken Windhounds and a variety of mixed breed dogs. The MDR1 TEST is now available and provides the following benefits: 1. it enables vets and breeders to use alternative medications for the prevention and treatment of parasite infections 2. it helps breeders to control the spread of the MDR1 mutation within the dog population. To test your dog we need a DNA sample obtained by buccal brush, which is available from us free of charge. For further information please visit LABOKLIN where you can read more and download an order form. Breeders
can request buccal swabs by emailing me: makki@laboklin.co.uk
or ringing me on 0161 282 3066 LIST OF
DRUGS THAT CAUSE SENSITIVITY TO DOGS AFFECTED BY MDR1 mutation UPDATE MAY 07 Dear Collie friends, We have created a webside (http://www.mdr1-defekt.de/index.php?lang=EN ) in order to help respectable breeders to consider, among other health aspects, also the “MDR1 defect” as a breeding criterion for amateur breeding. With affected dogs (MDR1 -/-) this genetic defect leads to the toxicity of various drug substances according to the latest scientific findings. For full information regarding the MDR1 defect, please click on this link Veterinärmedizinischen Universität Gießen. The initiators of this website therefore offer dog owners the following service free of charge: All dog owners (not only breeders) can publish the MDR1 test result and – if known- all other data known or relevant for breeding in the respective category for that breed. The webside has a lot international traffic and we hope that you have tested your dogs on MDR1 and send us the dates of your Collies too. We were not licensed to give informations about medicine products on our webside. We hope you understand that. Under the buttom publication you found some lecture you can google. We hope to hear from you.- Greetings Sandra Schäfer (webmaster@mdr1-defekt.de) |