J Vet Sci.  2010 Dec;11(4):341-344. 10.4142/jvs.2010.11.4.341.

Novel insertion mutation of ABCB1 gene in an ivermectin-sensitive Border Collie

• Han JI
• Son HW
• Park SC
• Na KJ

• KMID: 1072184
• DOI: http://doi.org/10.4142/jvs.2010.11.4.341

Abstract

P-glycoprotein (P-gp) is encoded by the ABCB1 gene and acts as an efflux pump for xenobiotics. In the Border Collie, a nonsense mutation caused by a 4-base pair deletion in the ABCB1 gene is associated with a premature stop to P-gp synthesis. In this study, we examined the full-length coding sequence of the ABCB1 gene in an ivermectin-sensitive Border Collie that lacked the aforementioned deletion mutation. The sequence was compared to the corresponding sequences of a wild-type Beagle and seven ivermectin-tolerant family members of the Border Collie. When compared to the wild-type Beagle sequence, that of the ivermectin-sensitive Border Collie was found to have one insertion mutation and eight single nucleotide polymorphisms (SNPs) in the coding sequence of the ABCB1 gene. While the eight SNPs were also found in the family members' sequences, the insertion mutation was found only in the ivermectin-sensitive dog. These results suggest the possibility that the SNPs are species-specific features of the ABCB1 gene in Border Collies, and that the insertion mutation may be related to ivermectin intolerance.

Keyword

ABCB1; Border Collie; insertion mutation; polymorphism

MeSH Terms

ATP-Binding Cassette Transporters/*genetics
Animals
Depression/chemically induced
Dogs/*genetics
Female
Ivermectin/*adverse effects
Male
Mutagenesis, Insertional/*genetics
Polymorphism, Single Nucleotide/genetics
Sialorrhea/chemically induced

Figure

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  Fig. 1 Pedigree analysis showing the relationships of the ivermectin-sensitive Border Collie and its seven family members. The black square indicates the ivermectin-sensitive Border Collie.

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  Fig. 2 Diagram showing the location of mutations in the coding sequence of the ABCB1 gene and P-glycoprotein (P-gp). The arrow indicates the position of the insertion mutation and arrowheads show the positions of single nucleotide polymorphisms. Underbars indicate the positions of insertion or substitution of nucleotides in the ABCB1 gene or amino acids in the P-gp molecule.

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