MDR1-deficient genotype in Collie dogs hypersensitive to the P-glycoprotein substrate ivermectin.

@article{Roulet2003MDR1deficientGI,
  title={MDR1-deficient genotype in Collie dogs hypersensitive to the P-glycoprotein substrate ivermectin.},
  author={Alain Roulet and Olivier Puel and Stéphane Gesta and J. F. Lepage and Marlene Drag and Mark D. Soll and Michel Alvinerie and Thierry Pineau},
  journal={European journal of pharmacology},
  year={2003},
  volume={460 2-3},
  pages={
          85-91
        }
}
Novel insertion mutation of ABCB1 gene in an ivermectin-sensitive Border Collie
TLDR
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, is suggested.
Presence of the ABCB1 (MDR1) deletion mutation causing ivermectin hypersensitivity in certain dog breeds in Belgium.
TLDR
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The neurotoxicological potential of different macrocyclic lactones as well as their treatment options in MDR1 mutant dogs are reviewed and discussed.
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TLDR
It is found that in vivo both macrocyclic lactone compounds are substrates of P-glycoprotein and that these strongly accumulate in the brain of mdr1a,b(-/-) knockout mice compared with wild-type mice at therapeutic doses of 12mg/kg selamectin and 0.2 mg/kg ivermectin.
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TLDR
The results indicated that the mutation was present in the Australian Shepherd, Collie, Shetland Sheepdog and Swiss White Shepherd, but was not detected in the Bearded Collies, Border Collies and German Shepherds of this study, which is in accordance with the findings in similar breed populations of other countries.
Frequency of the nt230 (del4) MDR1 mutation in Collies and related dog breeds in Germany.
TLDR
Considering the predominant role of MDR1 P-glycoprotein in drug disposition and in particular for blood-brain barrier protection, MDR 1 genotype-based breeding programs are recommended for improving the safety of drug therapy in these canine breeds.
Analysis of the Canine mdr1−1Δ Mutation in the Dog Breed Elo
TLDR
To determine whether the mdr1-1Delta mutation could be found in the newly bred German dog breed Elo which is based amongst other breeds on Old English sheepdogs, 177 blood samples representative for the Elo breed were collected.
Genotypic and allelic frequencies of MDR1 gene in dogs in Italy
TLDR
The results support the usefulness of this genetic analysis to optimise medical care in dogs at risk of multidrug resistance and to create an objective basis in breeding programme definition and in the risk evaluation in different breeds.
The ABCB1-1Delta mutation is not responsible for subchronic neurotoxicity seen in dogs of non-collie breeds following macrocyclic lactone treatment for generalized demodicosis.
TLDR
With the exception of one dog, the observed neurotoxicity could not be attributed to the ABCB1-1Delta mutation, and possible explanations for the adverse reactions observed include pharmacological interactions, excessively high doses, polymorphisms in P-gp expression, uncharacterized mutations in theABCB1 gene or in another gene, or phenomena unrelated to the SML-P-gp interaction.
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TLDR
A deletion mutation of the mdr1 gene is reported that is associated with ivermectin sensitivity and results in a frame shift, generating several stop codons that prematurely terminate P-gp synthesis.
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A restriction fragment length polymorphism is described that is able to predict which animals will be deficient in P-glycoprotein, confirming at the genetic level a heterogeneous population of this mouse strain.
P-glycoprotein deficiency in a subpopulation of CF-1 mice enhances avermectin-induced neurotoxicity.
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It is likely that this protein, found in human brain endothelium, is highly conserved in the human population, as this protein showed abundant levels of P-glycoprotein in these tissues and tolerated doses of abamectin at least 50-fold the minimum toxic dose in the sensitive subgroup.
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TLDR
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TLDR
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Human (MDR1) and mouse (mdr1, mdr3) P-glycoproteins can be distinguished by their respective drug resistance profiles and sensitivity to modulators.
TLDR
Analysis of the specific drug resistance profiles encoded by each P-gp for colchicine, adriamycin, vinblastine, and actinomycin D revealed overlapping but distinct patterns of drug resistance for the three isoforms, indicating that the three P- gp isoforms have specific and distinguishable functional characteristics with respect to interactions with drugs and modulators.
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