MDR 1 Gene Defect/Ivermectin Sensitivity in Collies and other breeds.

Update-Info on Emeprid 

Subject: RE: Emeprid 

The drug metoclopramide has been used to treat nausea, vomiting, and post operative gastrointestinal stasis in dogs in the United States for decades (brand name in the United States REGLAN) but has only recently been introduced in Europe under the brand name EMEPRID.  At high doses, the drug can cause changes in mentation and behavior in ANY breed of dog.  Despite the 1000’s (tens of 1000’s) of doses of metoclopramide administered to dogs in the U.S. over the past 20+ years, this drug has not previously been reported to cause problems in Collies or other herding breed dogs. We have attempted to get additional information about the cause of death in this dog and have not been able to do so.  We will continue to try to investigate this report. 

Sincerely,Katrina Mealey DVM PhDDACVIM, DACVCP
College of Veterinary Medicine
Washington State University
Please read EACA INFORMATION on MDR1 and updated drugs list. [Updated Sept 2010]

MDR 1 - Important information July 2009

Sharon Vanderlip response on MDR1

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.
In studies performed so far in other countries Rough collies, Shetland Sheepdogs, Old English Sheepdog, German Shepherds and Australian Sheepdogs have been most commonly affected. Thus at the University of Bristol and working with colleagues at the Washington State University,in the USA, we are currently trying to find how likely these breeds are to have the defective gene with in the UK.

Simon.Tappin@bristol.ac.uk or by telephone (0117 928 9420).

Thank you once again for you time and help, hopefully this project will help us work out the severity of this problem in the UK and therefore allow vets to treat illnesses more effectively.

This work will hopefully be presented in abstract form at the British Small Animal Veterinary Association meeting in April [08] next year and hopefully should be submitted as a paper to the journal of Small Animal Practice in the near future. I realise this information is not readily accessible to the dog owning public so if there are breed club newsletters or other similar publications you know of that would be interested in our results, please don't hesitate to contact me.

MDR1 & other collie health problems also covered by Collie Breed Clubs - CLICK HERE

Received from
Dr Mansour Makki
LABOKLIN [UK]
61 Mouldsworth Avenue
MANCHESTER
M20 1GG

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
Cost of test is £65 but this may be reduced in the near future.

LIST OF DRUGS THAT CAUSE SENSITIVITY TO DOGS AFFECTED BY MDR1 mutation
IVERMECTINS
DIGOXIN
VINCRISTINE
DOXORUBICIN
CYCLOSPORIN A
GREPAFLOXACIN
DEXAMETHASONE
LOPERAMIDE

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)