Identification of a nonsense mutation in feline ABCB1

J Vet Pharmacol Ther. 2015 Oct;38(5):429-33. doi: 10.1111/jvp.12212. Epub 2015 Feb 9.

Abstract

The aim of this study was to sequence all exons of the ABCB1 (MDR1) gene in cats that had experienced adverse reactions to P-glycoprotein substrate drugs (phenotyped cats). Eight phenotyped cats were included in the study consisting of eight cats that experienced central nervous system toxicosis after receiving ivermectin (n = 2), a combination product containing moxidectin and imidacloprid (n = 3), a combination product containing praziquantel and emodepside (n = 1) or selamectin (n = 2), and 1 cat that received the product containing praziquantel and emodepside but did not experience toxicity (n = 1). Fifteen exons contained polymorphisms and twelve exons showed no variation from the reference sequence. The most significant finding was a nonsense mutation (ABCB11930_1931del TC) in one of the ivermectin-treated cats. This cat was homozygous for the deletion mutation. All of the other phenotyped cats were homozygous for the wild-type allele. However, 14 missense mutations were identified in one or more phenotyped cats. ABCB11930_1931del TC was also identified in four nonphenotyped cats (one homozygous and three heterozygous for the mutant allele). Cats affected by ABCB11930_1931del TC would be expected to have a similar phenotype as dogs with the previously characterized ABCB1-1Δ mutation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / drug effects
  • ATP Binding Cassette Transporter, Subfamily B / genetics*
  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • Animals
  • Cat Diseases / chemically induced
  • Cats / genetics*
  • Cats / metabolism
  • Central Nervous System Diseases / chemically induced
  • Cloning, Molecular
  • Codon, Nonsense / genetics*
  • Depsipeptides / adverse effects
  • Exons / genetics
  • Homozygote
  • Imidazoles / adverse effects
  • Ivermectin / adverse effects
  • Macrolides / adverse effects
  • Neonicotinoids
  • Nitro Compounds / adverse effects
  • Polymorphism, Single Nucleotide
  • Praziquantel / adverse effects
  • Sequence Analysis, DNA / veterinary

Substances

  • ATP Binding Cassette Transporter, Subfamily B
  • Codon, Nonsense
  • Depsipeptides
  • Imidazoles
  • Macrolides
  • Neonicotinoids
  • Nitro Compounds
  • imidacloprid
  • Praziquantel
  • Ivermectin
  • moxidectin
  • emodepside