The „Ivermectin Sensitivity“ (MDR1 gene defect)
Avermectins are a class of natural products with broad antiparasitic activity. Ivermectin, a prominent member of the avermectin family, is a drug that is used extensively in veterinary medicine to treat infections caused by nematode and arthropod parasites. Although ivermectin is generally safe for use in domestic animals, in the 1980s a number of clinical cases with neurological manifestation have been reported after ivermectin treatment. Neurotoxic symptoms include mydriasis, tremors, ataxia and anorexia. These symptoms occur at doses that are 1/200th of the dose required to cause toxicity in other dogs. Neurological manifestations of ivermectin in susceptible dogs also include hypersalivation, blindness, coma respiratory compromise and death.

The „Ivermectin Sensitivity“-affected breeds
Collie, Border Collie, Shetland Sheepdog, Australian Shepherd, English Shepherd, McNab, Old English Sheepdog, Longhaired Whippet, Silken Windhound

The „Ivermectin Sensitivity“- Mutation and trait of inheritance
The multidrug-transporter MDR1 is part of the blood-brain barrier and responsible for limiting the brain penetration of a range of compounds of different therapeutic classes. Ivermectin sensitive dogs exhibit a 4 bp deletion mutation of the mdr1 gene that results in a frame shift, generating several stop codons that prematurely terminate synthesis of the multidrug-resistance transporter MDR1. Dogs that are homozygous for the mutation display, due to a non-functional transporter the ivermectin sensitive phenotype. They can show enhanced absorption of ivermectin and other substrates e.g. Digoxin, Vincristine, Doxorubicin, Cyclosporin A, Grepafloxacin, Dexamethasone and Loperamide.
The MDR1 gene defect is inherited as an autosomal recessive condition. Heterozygous animals (carriers) do not show „ivermectin sensitivity“ and live normal lives. They are able to propagate the responsible mutation throughout the population however and it is therefore important that carrier animals are detected prior to breeding.
 
The „Ivermectin Sensitivity“- Mutation and trait of inheritance
The MDR1 gene defect can be detected, using molecular genetic testing techniques. By DNA testing the mutation can be shown directly. The testing is carried out by state of the art laboratory methods and therefore provides a very high accuracy. In general DNA tests can be done at any age. These tests identify both affected and carrier animals. The mutation can be shown directly, what clearly identifies homozygous affected animals. The genetic test offers the unique possibility to identify Ivermectin sensitive animals prior to treatment with Ivermectin.

Requirements
The test is performed out of EDTA whole blood (0.5 ml) or special cytobrushes. These cytobrushes are available upon request. Testing is performed a few times per week at Laboklin. The results are due about 1 week after arrival of the sample in our laboratory.