Ivermectin sensitivity in collies is associated with a deletion mutation of the mdr1 gene

Pharmacogenetics. 2001 Nov;11(8):727-33. doi: 10.1097/00008571-200111000-00012.


A subpopulation of collie dogs is extremely sensitive to neurotoxicity induced by ivermectin. The aim of this study was to determine the mechanistic basis for this phenomenon. The multi-drug-resistance gene (mdr1) encodes a large transmembrane protein, P-glycoprotein (P-gp), that is an integral part of the blood-brain barrier. P-gp functions as a drug-transport pump at the blood-brain barrier, transporting a variety of drugs from the brain back into the blood. Since ivermectin is a substrate for P-gp, we hypothesized that ivermectin-sensitive collies had altered mdr1 expression compared with unaffected collies. We report a deletion mutation of the mdr1 gene that is associated with ivermectin sensitivity. The 4-bp deletion results in a frame shift, generating several stop codons that prematurely terminate P-gp synthesis. Dogs that are homozygous for the deletion mutation display the ivermectin-sensitive phenotype, while those that are homozygous normal or heterozygous do not display increased sensitivity to ivermectin.

Publication types

  • Comparative Study

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • Administration, Oral
  • Animals
  • Antinematodal Agents / administration & dosage
  • Antinematodal Agents / adverse effects
  • Base Sequence
  • Dog Diseases / genetics
  • Dog Diseases / prevention & control
  • Dogs / genetics*
  • Female
  • Frameshift Mutation / genetics*
  • Gene Deletion*
  • Genes, MDR / genetics*
  • Ivermectin / administration & dosage
  • Ivermectin / adverse effects*
  • Ivermectin / therapeutic use
  • Male
  • Molecular Sequence Data
  • Nematode Infections / genetics
  • Nematode Infections / prevention & control
  • Nematode Infections / veterinary


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antinematodal Agents
  • Ivermectin