Review of prevalence, genetic aspects and adverse effects of the mdr1-1Delta mutation in dogs.

Abstract

A mutation in the canine MDR1 gene causes multiple drug sensitivity in dog breeds of the Collie lineage. Dogs with this genetic defect show severe neurotoxic adverse effects if they are treated with particular drugs. Clinical signs depending on the administered drug and its concentration vary from mild toxicosis with salivation and disorientation to severe effects with coma and finally death of the dog. Drugs which provoke adverse effects are structurally different. Although they are used for many different indications, all of these drugs are substrates of a transporting protein encoded by the MDR1 gene. This P-glycoprotein loses its normal protecting function at the tissue barriers in dogs with the mdrl-1Delta mutation. This article gives a short overview about the present state of analyses regarding the canine MDR1 gene. The genetic background, effects and prevalence in affected dog breeds of the mdrl-1Delta mutation are summarized. On the one hand, the overview might help practical veterinarians to understand the aetiology of drug sensitivity in dogs with the mdrl-1Delta mutation, and on the other hand, it might point out appendages for future research works about the canine MDR1 gene as well as for breeding strategies in affected dog breeds.