Novel insertion mutation of ABCB1 gene in an ivermectin-sensitive Border Collie.
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.
Veterinary Laboratory Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju 361-763, Korea.
Jae-Ik
JI
Han
Hyoung-Won
HW
Son
Seung-Cheol
SC
Park
Ki-Jeong
KJ
Na
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000818:Animals; D003863:Depression / Q000139:chemically induced; D004285:Dogs / Q000235:genetics*; D005260:Female; D007559:Ivermectin / Q000009:adverse effects*; D008297:Male; D016254:Mutagenesis, Insertional / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012798:Sialorrhea / Q000139:chemically induced
D018528:ATP-Binding Cassette Transporters; D007559:Ivermectin