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Urinary cortisol metabolites are reduced in MDR1 mutant dogs in a pilot targeted GC-MS urinary steroid hormone metabolome analysis.
J Vet Pharmacol Ther
May 2022
Institute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Justus Liebig University Giessen, Giessen, Germany.
P-glycoprotein (P-gp) is the gene product of the multidrug resistance gene (MDR1, syn. ABCB1) that normally restricts the transfer of cortisol across the blood-brain barrier. In the absence of P-gp, cortisol access to the hypothalamus is increased and, by feedback inhibition, this finally leads to lower endogenous plasma cortisol levels in dogs with homozygous nt230(del4) MDR1 mutation (MDR1 mutant dogs).
View Article and Find Full Text PDFDetection of the 1930_1931del TC Mutation in Two Suspected Ivermectin-Sensitive Cats and Their Relatives by a Novel TaqMan Allelic Discrimination Assay.
Front Vet Sci
February 2022
Faculty of Veterinary Medicine, Institute of Pharmacology and Toxicology, Justus Liebig University Giessen, Giessen, Germany.
The multidrug resistance gene MDR1 (syn. ABCB1) encodes for the multidrug efflux transporter P-glycoprotein (P-gp), which is highly expressed at the blood-brain barrier and protects the brain from potentially neurotoxic compounds, such as ivermectin. MDR1 mutation in dogs is known to be linked to dramatically increased brain accumulation of ivermectin and life-threatening neurological toxicity.
View Article and Find Full Text PDFBreed distribution of the nt230(del4) MDR1 mutation in dogs.
Vet J
July 2011
Institute of Pharmacology and Toxicology, Justus Liebig University of Giessen, Frankfurter Str. 107, D-35392 Giessen, Germany.
A 4-bp deletion mutation associated with multiple drug sensitivity exists in the canine multidrug resistance (MDR1) gene. This mutation has been detected in more than 10 purebred dog breeds as well as in mixed breed dogs. To evaluate the breed distribution of this mutation in Germany, 7378 dogs were screened, including 6999 purebred and 379 mixed breed dogs.
View Article and Find Full Text PDFDetection of the nt230(del4) MDR1 mutation in White Swiss Shepherd dogs: case reports of doramectin toxicosis, breed predisposition, and microsatellite analysis.
J Vet Pharmacol Ther
October 2007
Institute of Pharmacology and Toxicology, College of Veterinary Medicine, Justus-Liebig-University of Giessen, Giessen, Germany.
Development of a PCR-based diagnostic test detecting a nt230(del4) MDR1 mutation in dogs: verification in a moxidectin-sensitive Australian Shepherd.
J Vet Pharmacol Ther
February 2005
Institute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Justus-Liebig-University of Giessen, Giessen, Germany.
A subpopulation of dogs of the Collie and Australian Shepherd breeds show increased sensitivity to central nervous actions of ivermectin, doramectin, loperamide, and probably several other drugs. The molecular background for this greater sensitivity is a nonsense mutation in the MDR1 efflux pump, which is part of the functional blood-brain barrier and normally limits drug penetration into the brain. This report describes a rapid PCR-based method for detection of this nt230(del4) MDR1 mutation using a small amount of genomic DNA from blood cells.
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