MDR1 in Rough Collies

It is now accepted that collie breeds appear to be hypersensitive to certain drugs. The problem first became apparent when several collies died of Ivermectin poisoning

Genetic studies have documented the MDR gene deletion in 10 breeds.  The gene deletion is widespread in collies, with 30% being affected (homozygous) and 40% being carriers (heterozygous). Its frequency is much lower in other herding breeds of collie lineage, such as the Shetland sheepdog (8.4% of dogs tested carried the mutation), Old English sheepdog (3.6%), and Australian sheepdog (16.6%). Because of different lineage, the gene deletion has not been found in Border collies, Bearded collies, or Australian cattle dogs. The deletion also occurs in 2 sighthound breeds, the longhaired whippet and the silken windhound, with suspicion that the mutation was introduced with Shetland sheepdog crosses. It has also been identified recently in white German Shepherd dogs. Dogs that are affected for the gene deletion readily show adverse effects from ivermectin and other P-glycoprotein substrate drugs at dosages that cause no adverse effects in normal dogs. Carriers (heterozygote dogs) may show toxicity at increased doses of substrate drugs, such as daily ivermectin.

The multi drug resistant (MDR1) gene is responsible for enabling the blood – brain barrier to function normally In MDR1 affected dogs this function is compromised allowing certain drug compounds to leak into the major organs of the body or across the blood – brain barrier where they enter the central nervous system. Symptoms include excessive salivation, ataxia, blindness, coma and breathing problems.

Testing for the gene is straightforward, but currently quite expensive (£65 per dog). The test involves taking 2 swabs from the mucosa in the dog’s mouth. The swabs are then allowed to air dry, before being put in a tube and sent to the laboratory. Laboklin provide the testing service at present.

Results

Normal – (+/+) The dog receives a healthy MDR1 gene from each of its parents and can therefore only pass on healthy genes. These dogs do not exhibit drug toxicity

Carrier – (+/-) The dog receives a normal gene from one parent and a defective gene from the other parent. Carriers do not develop multi drug sensitivity, but will pass normal and defected genes to its offspring, approximately 50% of the puppies would be expected to inherit a defective MDR1 gene.

Affected – (-/-) The dog receives a defective MDR1 gene from each of its parents. These dogs will display toxic reactions to a wide range of drug compounds.

 

MDR1 statistics in British Rough Collies (Laboklin & Bristol University)

May 2007 – April 2009

91 Dogs tested

Clear (+/+) - 14

Carriers (+/-) - 41

Affected (-/-) - 36

Known or potential problem drugs

Acepromazine

Butorphanol

Chinidin

Cyclosporin

Dexamethasone

Digoxin

Domperidone

Doxorubicin

Ebastine

Erythromycin

Etoposide

Grepafloxacin

Hydrocortisone

Ivermectin

Loperamide

Mitoxantrone

Morphine

Moxidectin

Ondansetron

Paclitaxe

Quinidine

Rifampicin

Selamectin

Sparfloxacin

Tacrolimus

Vinblastine

Vincristine