title: Allele-specific polymerase chain reaction diagnostic test for the functional MDR1 polymorphism in dogs.
abstract: The major multidrug transporter P-glycoprotein (Pgp) contributes to the barrier function of several tissues and organs, including the brain. In a subpopulation of Collies and seven further dog breeds, a 4 base pair deletion has been described in the Pgp-encoding MDR1 gene. This deletion results in the absence of a functional form of Pgp and loss of its protective function. Severe intoxication with the Pgp substrate ivermectin has been attributed to the genetically determined lack of Pgp. An allele-specific polymerase chain reaction (PCR)-based screening method has been developed to detect the mutant allele and to determine if a dog is homozygous or heterozygous for the mutation. Based on this validation, the allele-specific PCR proved to be a robust, reproducible and specific tool, allowing rapid determination of the MDR1 genotype of dogs of at risk breeds using blood samples or buccal swabs.
authors.affiliation: Institute of Pharmacology, Toxicology and Pharmacy, Ludwig Maximilians University, Munich, Germany.
authors.forename: Cordula
authors.initials: C
authors.lastname: Baars
authors.forename: Tosso
authors.initials: T
authors.lastname: Leeb
authors.forename: Thilo
authors.initials: T
authors.lastname: von Klopmann
authors.forename: Andrea
authors.initials: A
authors.lastname: Tipold
authors.forename: Heidrun
authors.initials: H
authors.lastname: Potschka
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000302:isolation & purification; D000483:Alleles; D000818:Animals; D001947:Breeding; D004285:Dogs / Q000235:genetics*; D019450:Genes, MDR / Q000235:genetics*; D005838:Genotype; D007559:Ivermectin / Q000009:adverse effects; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods / Q000662:veterinary*; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA / Q000662:veterinary
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007559:Ivermectin