title: Identification of a nonsense mutation in feline ABCB1.
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.
authors: Program in Individualized Medicine, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USA.
authors: K L
authors: KL
authors: Mealey
authors: Program in Individualized Medicine, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USA.
authors: N S
authors: NS
authors: Burke
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002371:Cat Diseases / Q000139:chemically induced; D002415:Cats / Q000235:genetics* / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000139:chemically induced; D003001:Cloning, Molecular; D018389:Codon, Nonsense / Q000235:genetics*; D047630:Depsipeptides / Q000009:adverse effects; D005091:Exons / Q000235:genetics; D006720:Homozygote; D007093:Imidazoles / Q000009:adverse effects; D007559:Ivermectin / Q000009:adverse effects; D018942:Macrolides / Q000009:adverse effects; D000073943:Neonicotinoids; D009574:Nitro Compounds / Q000009:adverse effects; D020641:Polymorphism, Single Nucleotide; D011223:Praziquantel / Q000009:adverse effects; D017422:Sequence Analysis, DNA / Q000662:veterinary
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D018389:Codon, Nonsense; D047630:Depsipeptides; D007093:Imidazoles; D018942:Macrolides; D000073943:Neonicotinoids; D009574:Nitro Compounds; C082359:imidacloprid; D011223:Praziquantel; D007559:Ivermectin; C027837:moxidectin; C468987:emodepside