19
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Occurrence of MDR1 1-delta mutation in herding dog breeds in Portugal

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The impact of drug transporters in veterinary medicine has been recognized in recent years. One of the most well-characterized is the product of the MDR1 gene, P-gp. A 4-bp deletion in the MDR1 gene known since 2001 has been described to affect herding dog breeds. Since many used drugs in veterinary medicine are substrates for P-gp, including the macrocyclic lactones, such as avermectins, this 4-bp deletion causes a pathological condition known as “ivermectin toxicosis.” For this reason, it is important to determine the animal status concerning this mutation. In Portugal, the information of the occurrence of this mutation in our breeds is limited. The aim of the present study was to determine the occurrence of this mutation and evaluate its association with Portuguese and non-Portuguese dog breeds in Portugal. To achieve this, a total of 105 animals were studied for the presence of the MDR1 4-bp deletion, 23 of which were from Barbado da Terceira, 10 from Cão da Serra d'Aires, 55 belonging to breeds known to carry the mutation (Australian Shepperd, Border Collie and others) and 17 to other breeds (Labrador Retriever, Jack Russel, and others). Despite the small sample size, we observed the presence of the MDR1 1—delta mutation in previously described breeds and identified this mutation in Barbado da Terceira breed for the first time.

          Related collections

          Most cited references18

          • Record: found
          • Abstract: found
          • Article: not found

          A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants

          Chinese hamster ovary cells selected for resistance to colchicine display pleiotropic cross-resistance to a wide range of amphiphilic drugs. The drug-resistant phenotype is due to a membrane alteration which reduces the rate of drug permeation. Surface labelling studies reveal that drug-resistant Chinese hamster ovary cell membranes possess a carbohydrate-containing component of 170 000 daltons apparent molecular weight which is not observed in wild type cells. Through studies of the metabolic incorporation of carbohydrate and protein precursors, and through the use of selective proteolysis, this component is shown to be a cell surface glycoprotein. Since this glycoprotein appears unique to mutant cells displaying altered drug permeability, we have designated it the P glycoprotein. The relative amount of surface labelled P glycoprotein correlates with the degree of drug resistance in a number of independent mutant and revertant clones. A similar high molecular weight glycoprotein is also present in drug-resistant mutants from another hamster cell line. Observations on the molecular basis of pleiotropic drug resistance are interpreted in terms of a model wherein certain surface glycoproteins control drug permeation by modulating the properties of hydrophobic membrane regions...
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Ivermectin sensitivity in collies is associated with a deletion mutation of the mdr1 gene.

            A subpopulation of collie dogs is extremely sensitive to neurotoxicity induced by ivermectin. The aim of this study was to determine the mechanistic basis for this phenomenon. The multi-drug-resistance gene (mdr1) encodes a large transmembrane protein, P-glycoprotein (P-gp), that is an integral part of the blood-brain barrier. P-gp functions as a drug-transport pump at the blood-brain barrier, transporting a variety of drugs from the brain back into the blood. Since ivermectin is a substrate for P-gp, we hypothesized that ivermectin-sensitive collies had altered mdr1 expression compared with unaffected collies. We report a deletion mutation of the mdr1 gene that is associated with ivermectin sensitivity. The 4-bp deletion results in a frame shift, generating several stop codons that prematurely terminate P-gp synthesis. Dogs that are homozygous for the deletion mutation display the ivermectin-sensitive phenotype, while those that are homozygous normal or heterozygous do not display increased sensitivity to ivermectin.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Breed distribution and history of canine mdr1-1Delta, a pharmacogenetic mutation that marks the emergence of breeds from the collie lineage.

              A mutation in the canine multidrug resistance gene, MDR1, has previously been associated with drug sensitivities in two breeds from the collie lineage. We exploited breed phylogeny and reports of drug sensitivity to survey other purebred populations that might be genetically at risk. We found that the same allele, mdr1-1Delta, segregated in seven additional breeds, including two sighthounds that were not expected to share collie ancestry. A mutant haplotype that was conserved among affected breeds indicated that the allele was identical by descent. Based on breed histories and the extent of linkage disequilibrium, we conclude that all dogs carrying mdr1-1Delta are descendants of a dog that lived in Great Britain before the genetic isolation of breeds by registry (ca. 1873). The breed distribution and frequency of mdr1-1Delta have applications in veterinary medicine and selective breeding, whereas the allele's history recounts the emergence of formally recognized breeds from an admixed population of working sheepdogs.
                Bookmark

                Author and article information

                Contributors
                Journal
                Front Vet Sci
                Front Vet Sci
                Front. Vet. Sci.
                Frontiers in Veterinary Science
                Frontiers Media S.A.
                2297-1769
                03 October 2022
                2022
                : 9
                : 990884
                Affiliations
                [1] 1CIISA – Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon , Lisbon, Portugal
                [2] 2Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS) , Lisbon, Portugal
                Author notes

                Edited by: Arturo Anadón, Complutense University of Madrid, Spain

                Reviewed by: Jose P. Oliveira-Filho, São Paulo State University, Brazil; Gracia Merino, Universidad de León, Spain; Michael J. Myers, Center for Veterinary Medicine (FDA), United States

                *Correspondence: Berta São Braz bsaobraz@ 123456fmv.ulisboa.pt

                This article was submitted to Veterinary Pharmacology and Toxicology, a section of the journal Frontiers in Veterinary Science

                †These authors have contributed equally to this work and share first authorship

                Article
                10.3389/fvets.2022.990884
                9574212
                36262528
                a89669d3-200a-4e72-85cd-c625672dd636
                Copyright © 2022 Barroso, Grilo, Aguiar, Aires da Silva and São Braz.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 10 July 2022
                : 14 September 2022
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 23, Pages: 6, Words: 3662
                Funding
                Funded by: Fundação para a Ciência e a Tecnologia, doi 10.13039/501100001871;
                Categories
                Veterinary Science
                Original Research

                mdr1 mutation,herding dogs,portugal,portuguese breeds,pharmacotherapy

                Comments

                Comment on this article