Introduction

The multidrug resistance (MDR1) gene encodes P-glycoprotein, which is an ATP-dependent cellular efflux pump and an essential part of the blood brain barrier. Normal P-glycoprotein expression limits the uptake of many drugs and toxins into the central nervous system; substrates include ivermectin, loperamide, digoxin, vincristine and opiates. Mutations in the MDR gene lead to abnormal P-glycoprotein expression and unexpected drug toxicity. Abnormal MDR expression was first associated with the CNS accumulation of ivermectin in Rough collies. However, the mutation has been found in related collie breeds and a number of other P-glycoprotein substrates have been associated with toxicity. The aim of this study was to investigate the prevalence of the MDR1 mutation within the United Kingdom.

Materials and Methods

DNA was collected, with owner consent, using buccal swabs or residual blood from 642 dogs. Dogs from eight pastoral (250 dogs), nine gundog (156 dogs), six hound (53 dogs), three terrier (51 dogs), four working (49 dogs), five toy (48 dogs) and five utility breeds (35 dogs) were investigated. Using previously published methods the MDR gene was amplified using PCR and reaction products were analyzed by amplified fragment length polymorphism gel (AFLP) to determine the MDR1 genotype.

Results

The MDR mutation was found in 6 breeds which were all pastoral breeds of collie descent. The mutation was not present in the remaining 33 breeds. See Figure 1.

Conclusions

The MDR mutation is present in UK pastoral (herding) breeds and although the sample numbers are small the prevalence of the mutant MDR allele is higher in Australian shepherds, Rough and Smooth collies and Shetland sheepdogs, when compared to previous studies from the USA, France and Germany. Care should therefore be taken when treating dogs of susceptible breeds to avoid potential drug toxicity.

Figure 1. *Allele % is the percentage of affected genes in the sample group.