• 1.

    Mealey KL. Therapeutic implications of the MDR-1 gene. J Vet Pharmacol Ther 2004;27:257264.

  • 2.

    Mealey KL, Greene S, Bagley R, et al. P-glycoprotein contributes to the blood-brain, but not blood-cerebrospinal fluid, barrier in a spontaneous canine p-glycoprotein knockout model. Drug Metab Dispos 2008;36:10731079.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Coelho JC, Tucker R, Mattoon J, et al. Biliary excretion of technetium-99m-sestamibi in wild-type dogs and in dogs with intrinsic (ABCB1-1∆ mutation) and extrinsic (ketoconazole treated) P-glycoprotein deficiency. J Vet Pharmacol Ther 2009;32:417421.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Mealey KL, Bentjen SA, Gay JM, et al. Ivermectin sensitivity in Collies is associated with a deletion mutation of the mdr1 gene. Pharmacogenetics 2001;11:727733.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Mealey KL, Burke NS. Identification of a nonsense mutation in feline ABCB1. J Vet Pharmacol Ther 2015;38:429433.

  • 6.

    Richards B, Skoletsky J, Shuber AP, et al. Multiplex PCR amplification from the CFTR gene using DNA prepared from buccal brushes/swabs. Hum Mol Genet 1993;2:159163.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Merola VM, Eubig PA. Toxicology of avermectins and milbemycins (macrocyclic lactones) and the role of P-glycoprotein in dogs and cats. Vet Clin North Am Small Anim Pract 2018;48:9911012.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Mealey KL. How should I treat dogs and cats with MDR1 mutations? Ther Briefs 2016,3:1223.

  • 9.

    Jourdan G, Boyer G, Raymond-Letron I, et al. Intravenous lipid emulsion therapy in 20 cats accidentally overdosed with ivermectin. J Vet Emerg Crit Care (San Antonio) 2015;25:667671.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10.

    Wright HM, Chen AV, Talcott PA, et al. Intravenous fat emulsion as treatment for ivermectin toxicosis in three dogs homozygous for the ABCB1-1∆ gene mutation. J Vet Emerg Crit Care (San Antonio) 2011;21:666672.

    • Crossref
    • Search Google Scholar
    • Export Citation

Advertisement

Role of an ABCB1 1930_1931del TC gene mutation in a temporal cluster of macrocyclic lactone–induced neurologic toxicosis in cats associated with products labeled for companion animal use

View More View Less
  • From the Program in Individualized Medicine, College of Veterinary Medicine, Washington State University, Pullman, WA 99164.

Abstract

OBJECTIVE

To determine whether ABCB11930_1931del TC predisposed cats to macrocyclic-lactone toxicosis and the frequency of the ABCB11930_1931del TC gene mutation in banked feline DNA samples.

SAMPLE

DNA samples from 5 cats presented for neurologic clinical signs presumed to be caused by exposure to macrocyclic lactones and 1,006 banked feline DNA samples.

PROCEDURES

The medical history pertaining to 5 cats was obtained from veterinarians who examined, treated, or performed necropsies on them. The DNA from these 5 cats and 1,006 banked feline samples were analyzed for the presence of the ABCB11930_1931del TC genotype.

RESULTS

4 of the 5 cats with neurologic signs presumed to be associated with macro-cyclic-lactone exposure were homozygous for ABCB11930_1931del TC. The other cat had unilateral vestibular signs not typical of macrocyclic-lactone toxicosis. The distribution of genotypes from the banked feline DNA samples was as follows: 0 homozygous for ABCB11930_1931del TC, 47 heterozygous for ABCB11930_1931del TC, and 959 homozygous for the wild-type ABCB1 allele. Among the 47 cats with the mutant ABCB1 allele, only 3 were purebred (Ragdoll, Russian Blue, and Siamese).

CONCLUSIONS AND CLINICAL RELEVANCE

Results suggested a strong relationship between homozygosity for ABCB11930_1931del TC and neurologic toxicosis after topical application with eprinomectin-containing antiparasitic products labeled for use in cats. Although this genotype is likely rare in the general cat population, veterinarians should be aware of this genetic mutation in cats and its potential for enhancing susceptibility to adverse drug reactions. (J Am Vet Med Assoc 2021;259:72–76)

Abstract

OBJECTIVE

To determine whether ABCB11930_1931del TC predisposed cats to macrocyclic-lactone toxicosis and the frequency of the ABCB11930_1931del TC gene mutation in banked feline DNA samples.

SAMPLE

DNA samples from 5 cats presented for neurologic clinical signs presumed to be caused by exposure to macrocyclic lactones and 1,006 banked feline DNA samples.

PROCEDURES

The medical history pertaining to 5 cats was obtained from veterinarians who examined, treated, or performed necropsies on them. The DNA from these 5 cats and 1,006 banked feline samples were analyzed for the presence of the ABCB11930_1931del TC genotype.

RESULTS

4 of the 5 cats with neurologic signs presumed to be associated with macro-cyclic-lactone exposure were homozygous for ABCB11930_1931del TC. The other cat had unilateral vestibular signs not typical of macrocyclic-lactone toxicosis. The distribution of genotypes from the banked feline DNA samples was as follows: 0 homozygous for ABCB11930_1931del TC, 47 heterozygous for ABCB11930_1931del TC, and 959 homozygous for the wild-type ABCB1 allele. Among the 47 cats with the mutant ABCB1 allele, only 3 were purebred (Ragdoll, Russian Blue, and Siamese).

CONCLUSIONS AND CLINICAL RELEVANCE

Results suggested a strong relationship between homozygosity for ABCB11930_1931del TC and neurologic toxicosis after topical application with eprinomectin-containing antiparasitic products labeled for use in cats. Although this genotype is likely rare in the general cat population, veterinarians should be aware of this genetic mutation in cats and its potential for enhancing susceptibility to adverse drug reactions. (J Am Vet Med Assoc 2021;259:72–76)

Contributor Notes

Address correspondence to Dr. Mealey (kmealey@wsu.edu).