Study of the mutant MDR1 allele in four Collie breeds in Italy

The P-Glycoprotein is an ATP-dependent drug tran- sponder (P-gp) encoded by the MDR1 gene, also known as ABCB1. Lack of the P-gp protein causes multidrug resistance 1 in the hematoencephalic bar- rier, leading to neurotoxicosis after administration of several drugs (ex: ivermectin and P-glycoprotein sub- states). Within this study we analyzed a 4 bp deletion mutation that causes the introduction of several stop codons that eventually lead to the premature trunca- tion of P-gp. In the absence of mutations, the P-Gp protein binds to a variety of compounds/drugs in the endothelial cells, transporting them back into the bloodstream and consequently preventing their diffu- sion in the brain. The aim of the present work was to analyze the frequency of the mutant MDR1 allele in the four recognized Collie breeds (FCI; Canis famil- iaris). The four collie breeds analyzed where: Bearded C. (BEA), Border C. (BOR), Rough C. (ROU) and Smooth C. (SMO) for a total of 135 individuals (mean sex ratio M/F = 3/4). Allelic frequencies in the four breeds and their comparison were calculated using the SAS software. In the BEA group 100% of the subject were wt/wt, in the BOR 98.53 were wt/wt and 1.47% wt/del. In the ROU breed we recorded 16.13% wt/wt, 48.39% of wt/del and 35.48% of del/del. The tested SMO was wt/del. The differences were signi cantly different (P  0.05), however the BEA and SMO where represented only by 5 individuals in total. No differences were recorded in frequency of mutation in tested males and females analyzing the entire pop- ulation. In conclusion, our results demonstrated that notwithstanding the common phylogenetic origin of the breeds analyzed the MDR1 mutation has sig- ni cant different, leading to differential risk of drug response. These results further demonstrate, that the deletion can be easily tracked in pure breed collie of the different breeds allowing the planning of selective strategies aimed to improve animal health and genetic variability in small size canine populations.