Frequency of the nt230 (del4) MDR1 mutation in Collies and related dog breeds in Germany.
MDR1 (ABCB1) P-glycoprotein exerts a protective function in the blood-brain barrier thereby limiting the entry of many drugs and other xenobiotics to the central nervous system. A nonsense mutation has been described for Collies and related dog breeds which abolishes this function and is associated with increased susceptibility to neurotoxic side effects of several drugs including ivermectin, moxidectin and loperamide. In order to evaluate the occurrence and frequency of this nt230 (del4) MDR1 mutation in Germany, we screened 1500 dogs. Frequency of the homozygous mutated genotype was highest for Collies (33.0%), followed by Australian Shepherd (6.9%) and Shetland Sheepdog (5.7%). Thirty-seven percent of the Wäller dogs and 12.5% of the Old English Sheepdogs were heterozygous for the mutant MDR1 (-) allele. Considering the predominant role of MDR1 P-glycoprotein in drug disposition and in particular for blood-brain barrier protection, MDR1 genotype-based breeding programs are recommended for improving the safety of drug therapy in these canine breeds.
Geyer
J
J
Institute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Justus-Liebig-University of Giessen, Giessen, Germany.
Döring
B
B
Godoy
J R
JR
Leidolf
R
R
Moritz
A
A
Petzinger
E
E
D000818:Animals; D000890:Anti-Infective Agents; D001483:Base Sequence; D004247:DNA / Q000032:analysis; D004285:Dogs / Q000235:genetics*; D018432:Drug Resistance, Multiple / Q000235:genetics*; D016368:Frameshift Mutation / Q000235:genetics; D019450:Genes, MDR / Q000235:genetics*; D008969:Molecular Sequence Data; D010375:Pedigree; D016133:Polymerase Chain Reaction / Q000662:veterinary
D000890:Anti-Infective Agents; D004247:DNA