Mutation of MDR1 gene associated with multidrug sensitivity in Australian shepherds in Slovenia | [Mutacija gena MDR1, povezana s preobcutljI.stjo na razlicna zdravila pri Avstralskih ovcarjih v Sloveniji]
2007
Cotman, M., Ljubljana Univ. (Slovenia). Veterinary Fac. | Zabavnik-Piano, J.
The multidrug-resistance 1 (MDR1) transport protein plays an important protective role at blood-tissue barriers by limiting the entry of MDR1 protein substrates to brain, testis, fetus and other tissues. For subpopulation of Collies and related dog breeds increased susceptibility to neurotoxic side effects of several drugs including ivermectin, moxidectin and loperamide was detected. It was demonstrated that in ivermectin susceptible dogs the deletion mutation in MDR1 gene produces a frame shift resulting in the production of severly truncated non-functional MDR1 protein. In order to evaluate the occurrence and frequency of the mutated mdr1-1DELTA allele in the population of Australian Shepherds in Slovenia we have screened 10 dogs representing approximately one third of the Slovenian population. The results of our study indicate very high frequency of mdr1-1DELTA allele (70%) in Australian Shepherds in Slovenia. In 40% of studied population homozygous mutated genotype was determined. Considering the important role of MDR1 protein in drug disposition and blood-brain barrier protection, testing of the MDR1 genotypes and MDR1 genotype-based breeding programs are recommended for improving the safety of drug therapy with MDR1 protein substrates in Australian Shepherds.
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