OMIA:001402-9615 : Multidrug resistance 1, ABCB1-related in Canis lupus familiaris (dog) |
In other species: domestic cat , taurine cattle , goat
Categories: Homeostasis / metabolism phene
Links to possible relevant human trait(s) and/or gene(s) in OMIM: 171050 (gene) , 120080 (trait)
Single-gene trait/disorder: yes
Mode of inheritance: Autosomal incomplete dominant
Disease-related: yes
Key variant known: yes
Year key variant first reported: 2001
Cross-species summary: MDR1
Species-specific name: Ivermectin sensitivity
Species-specific description: Multidrug resistance 1 is caused by a lack of P-glycoprotein drug transporter in the blood-brain barrier, which is characterized by neurotoxicity after administration of certain drugs.
Inheritance: The mode of inheritance was initially considered as autosomal recessive. However, Mealey et al. (2003) reported a single dog, who was heterozugous for the ∆MDR1 [omia.variant:469], with increased toxicity of P-glycoprotein-substrate chemotherapeutic agents, and Mealey and Meurs (2008) suggest that 'heterozygous dogs appear to have an intermediate phenotype with respect to responses to avermectins'. Thus an incomplete dominant mode of inheritance may be considered.
Molecular basis: By cloning and sequencing a very likely candidate gene (based on knowledge of the biochemistry and physiology of the disorder) Mealey et al. (2001) identified the causative mutation as a 4 bp deletion (c.296_299del4; omia.variant:469) in the ABCB1 (MDR1) gene, which encodes P-glycoprotein drug transporter (P-gp). The deletion causes a frame shift, introducing several stop codons, which cause premature protein truncation. P-gp is an ATP-driven drug transporter that binds a variety of drugs in the endothelial cells and transports them back into the blood, preventing them from diffusing into the brain. P-gp is expressed in brain capillaries, renal proximal tubules, liver, small bowel, colon, placenta, and brain endothelium. P-gp is also expressed at high levels in tumor cells, allowing them to resist a spectrum of chemotherapeutic drugs (Mealey et al., 2001, Gramer et al., 2011). Han et al. (2010) reported a different causal mutation, c.73insAAT (omia.variant:607), in an ivermectin-sensitive Border Collie. However, this allele is reflected by the reference sequence CanFam3.1. Alves et al. (2011) reported a base substitution (c.-6-180T>G, (omia.variant:442) in intron 1 that "was significantly more frequent in epileptic [Border Collies] resistant to [phenobarbital] treatment than in epileptic BCs responsive to PB treatment". However, in a "multicentre retrospective, case-control study", Gagliardo et al. (2019) showed that there is no association between the likely causal variant c.-6-180T>G [omia.variant:442] and refractory epilepsy in a "multi-breed cohort of dogs".
Clinical features: In the 1980s, dogs of predominantly herding breeds were reported with adverse effects following drug administration. When these dogs are administered xenobiotics at an appropriate dose, the drug accumulates in the brain leading to severe neurotoxicity. Affected animals may present with generalised tremor, agitation, severe panting, hypersalivation, lethargy, disorientation, depression, mydriasis, loss of menace, loss of papillary light responses, blindness, seizures, proprioceptive ataxia, weakness, bradycardia, obtundation, recumbency and coma (Mealey et al., 2001; Bissonnette et al., 2009; Gaens et al., 2019). Mydriasis is suggested to be the most sensitive sign (Bissonnette et al., 2009). [IT thanks DVM student Hannah Edgell for contributions to this entry in April 2022]
Pathology: P-glycoprotein (P-gp) is an adenosine triphosphate driven drug transporter, encoded for by the ABCB1 gene. P-gp normally transports some chemotherapeutic agents (Vinca alkaloids, doxorubicin), immunosuppressants (cyclosporine, tacrolimus), macrocyclic lactone antiparasitic drugs (ivermectin, loperamide, milbemycin, selamectin, moxidectin), HIV-1 protease inhibitors, and steroid hormones. It is expressed in many tissues, including the liver, kidneys, and intestines, where it functions to reduce drug uptake from the gut and promote drug excretion in the bile duct and urine (Gramer et al., 2011). Moreover, it is a major component of the blood-brain barrier, thus is crucial in protecting the central nervous system from exposure to certain drugs (Schinkel et al., 1996). Dogs that are homozygous for causal ABCB1 mutations lack P-gp, and consequently are susceptible for certain drugs to penetrate into the brain, and accumulation of high drug levels in the brain leads to toxicity (Mealey, 2008). [IT thanks DVM student Hannah Edgell for contributions to this entry in April 2022]
Prevalence: In the USA, the frequency of the 4bp deletion allele [omia.variant:469] was reported as 56-75% in collies, 7% in Shetland sheepdogs, 29% in Australian shepherds, 1% in Border collies, 1% in old English sheepdogs, 20% in miniature Australian shepherds, 29% in longhaired whippets, 16% in silken windhounds, and 6% in German shepherds (Mealey and Meurs, 2008, Mealey, 2008). In Germany, the frequency of the same allele was reported as 59% in collies, 45% in longhaired whippets, 30% in Shetland sheepdogs, 24% in miniature Australian shepherds, 22% in Australian shepherds, 17% in Wällers, 14% in white Swiss shepherds, 4% in old English sheepdogs, 1% in Border collies, 8% in herding breed mixes, and 2% in mixed breeds (Gramer et al., 2011). Mizukami et al. (2013) developed a PCR-RFLP genotyping test for the c.-6-180T>G mutation [omia.variant:442], and in 472 Border Collies in Japan "demonstrated the frequencies of the T/T wild type, T/G heterozygote, and G/G mutant homozygote to be 60.0%, 30.3%, and 9.8%, respectively, indicating that the frequency of the mutant G allele is extremely high (24.9%) in Border Collies. The results suggest that this high mutation frequency of the mutation is likely to cause a high prevalence of phenobarbital-resistant epilepsy in Border Collies." Mizukami et al. (2016) reported the frequency of the 4bp deletion allele [omia.variant:469] as 0.002 in 500 Border collies in Japan. Lerdkrai et al. (2021) "clarified the prevalence of MDR1 nt230(del4) [omia.variant:469] in 263 dogs of eight purebred dog breeds in Thailand ... . Rough Collies, Australian Shepherds, Shetland Sheepdogs, and Old English Sheepdogs were affected by the mutation with mutant allelic frequencies of 57.14%, 12.82%, 11.28%, and 8.33%, respectively. ... However, the MDR1 nt230(del4) [omia.variant:469] was not identified in Border Collies, German Shepherds, White Swiss Shepherds, or Thai Ridgebacks.
Genetic testing: Silvestro et al. (2019) developed two methods for genotyping the deletion variant.
Breeds:
Australian Shepherd (Dog) (VBO_0200095),
Border Collie (Dog) (VBO_0200193),
Collie (Dog) (VBO_0200375),
Collie Rough (Dog) (VBO_0200376),
German Shepherd Dog (Dog) (VBO_0200577),
Huntaway (Dog) (VBO_0200683),
Long-Haired Whippet (Dog) (VBO_0200833),
McNab Shepherd (Dog) (VBO_0200872),
Miniature Australian Shepherd Dog (Dog) (VBO_0200881),
Mixed Breed (Dog) (VBO_0200902),
Old English Sheepdog (Dog) (VBO_0200969),
Shetland Sheepdog (Dog) (VBO_0201217),
Silken Windhound (Dog) (VBO_0201235),
Waller (Dog) (VBO_0201394),
White Swiss Shepherd Dog (Dog) (VBO_0201423).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).
Associated gene:
Symbol | Description | Species | Chr | Location | OMIA gene details page | Other Links |
---|---|---|---|---|---|---|
ABCB1 | ATP-binding cassette, sub-family B (MDR/TAP), member 1 | Canis lupus familiaris | 14 | NC_051818.1 (13507439..13410127) | ABCB1 | Homologene, Ensembl , NCBI gene |
Variants
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
OMIA Variant ID | Breed(s) | Variant Phenotype | Gene | Allele | Type of Variant | Source of Genetic Variant | Reference Sequence | Chr. | g. or m. | c. or n. | p. | Verbal Description | EVA ID | Year Published | PubMed ID(s) | Acknowledgements |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
607 | Border Collie (Dog) | Adverse reaction to certain drugs | ABCB1 | insertion, small (<=20) | Naturally occurring variant | CanFam3.1 | 14 | CanFam3.1 | published as c.73insAAT - the allele is reflected by the reference sequence CanFam3.1 and NM_001003215.2 as reference: g.13737172_13737174; c.73_75, p.N25; causality of this variant should be reviewed | 2010 | 21113104 | |||||
469 | Australian Shepherd (Dog) Border Collie (Dog) Collie (Dog) German Shepherd Dog (Dog) Long-Haired Whippet (Dog) Miniature Australian Shepherd Dog (Dog) Old English Sheepdog (Dog) Shetland Sheepdog (Dog) Silken Windhound (Dog) Waller (Dog) White Swiss Shepherd Dog (Dog) | Adverse reaction to certain drugs | ABCB1 | deletion, small (<=20) | Naturally occurring variant | CanFam3.1 | 14 | NC_006596.3:g.13726596_13726599del | NM_001003215.2:c.228_231del | NM_001003215.2:p.(D77Afs*16) | 2001 | 11692082 | Variant information initially gleaned from or confirmed by Donner et al. (2016) PLoS One 11:e0161005 and later updated to reflect HGVS nomenclature. | |||
442 | Border Collie (Dog) | Adverse reaction to certain drugs | ABCB1 | regulatory | Naturally occurring variant | CanFam3.1 | 14 | NC_006596.3:g.13742402A>C | published as Canfam2 chr14:16692274T>G, c.-6-180T>G, possible regulatory variant associated with resistance to phenobarbital treatment in epileptic Border Collies; an association between the variant and the phenotype was not supported in a different study: PMID: 31685133 | rs852787132 | 2011 | 21488961 | Genomic coordinates in CanFam3.1 and EVA ID provided by Zoe Shmidt and Robert Kuhn. |
Cite this entry
Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2024). OMIA:001402-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70
References
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2024 | Vaidhya, A., Ghildiyal, K., Rajawat, D., Nayak, S.S., Parida, S., Panigrahi, M. : |
Relevance of pharmacogenetics and pharmacogenomics in veterinary clinical practice: A review. Anim Genet 55:3-19, 2024. Pubmed reference: 37990577. DOI: 10.1111/age.13376. | |
2023 | Gedye, K., Poole-Crowe, E., Shepherd, M., Wilding, A., Parton, K., Lopez-Villalobos, N., Cave, N. : |
Prevalence of the ABCB1-1Δ gene mutation in a sample of New Zealand Huntaway dogs. N Z Vet J 71:133-136, 2023. Pubmed reference: 36786530. DOI: 10.1080/00480169.2023.2181238. | |
Massat, M.J., Myles, M., DeJong, K., Ballard, C., Drag, M., Malinski, T.J. : | |
Plasma chemistry reference intervals for adult multi-drug-resistance gene deficient Collies. Vet Clin Pathol 52:737-743, 2023. Pubmed reference: 37475133. DOI: 10.1111/vcp.13286. | |
Meadows, J.R.S., Kidd, J.M., Wang, G.D., Parker, H.G., Schall, P.Z., Bianchi, M., Christmas, M.J., Bougiouri, K., Buckley, R.M., Hitte, C., Nguyen, A.K., Wang, C., Jagannathan, V., Niskanen, J.E., Frantz, L.A.F., Arumilli, M., Hundi, S., Lindblad-Toh, K., Ginja, C., Agustina, K.K., André, C., Boyko, A.R., Davis, B.W., Drögemüller, M., Feng, X.Y., Gkagkavouzis, K., Iliopoulos, G., Harris, A.C., Hytönen, M.K., Kalthoff, D.C., Liu, Y.H., Lymberakis, P., Poulakakis, N., Pires, A.E., Racimo, F., Ramos-Almodovar, F., Savolainen, P., Venetsani, S., Tammen, I., Triantafyllidis, A., vonHoldt, B., Wayne, R.K., Larson, G., Nicholas, F.W., Lohi, H., Leeb, T., Zhang, Y.P., Ostrander, E.A. : | |
Genome sequencing of 2000 canids by the Dog10K consortium advances the understanding of demography, genome function and architecture. Genome Biol 24:187, 2023. Pubmed reference: 37582787. DOI: 10.1186/s13059-023-03023-7. | |
Mealey, K.L., Owens, J.G., Freeman, E. : | |
Canine and feline P-glycoprotein deficiency: What we know and where we need to go. J Vet Pharmacol Ther 46:1-16, 2023. Pubmed reference: 36326478. DOI: 10.1111/jvp.13102. | |
Mealey, K.L., Burke, N.S. : | |
Assessment of verdinexor as a canine P-glycoprotein substrate. J Vet Pharmacol Ther 46:264-267, 2023. Pubmed reference: 36924353. DOI: 10.1111/jvp.13123. | |
2022 | Beckers, E., Casselman, I., Soudant, E., Daminet, S., Paepe, D., Peelman, L., Broeckx, B.J.G. : |
The prevalence of the ABCB1-1Δ variant in a clinical veterinary setting: The risk of not genotyping. PLoS One 17:e0273706, 2022. Pubmed reference: 36037240. DOI: 10.1371/journal.pone.0273706. | |
Drag, M., Tielemans, E., Mitchell, E. : | |
Safety of oral afoxolaner formulated with or without milbemycin oxime in homozygous MDR1-deficient collie dogs. J Vet Pharmacol Ther 45:373-379, 2022. Pubmed reference: 35536118. DOI: 10.1111/jvp.13064. | |
2021 | Lerdkrai, C., Phungphosop, N. : |
Prevalence of the MDR1 gene mutation in herding dog breeds and Thai Ridgebacks in Thailand. Vet World 14:3015-3020, 2021. Pubmed reference: 35017851. DOI: 10.14202/vetworld.2021.3015-3020. | |
2020 | Soussa, R.W., Woodward, A., Marty, M., Cannon, C.M. : |
Breed is associated with the ABCB1-1Δ mutation in Australian dogs. Aust Vet J 98:79-83, 2020. Pubmed reference: 31743433. DOI: 10.1111/avj.12896. | |
2019 | Gaens, D., Leithäuser, C., Hamann, M., Geyer, J. : |
Adverse drug reactions after administration of emodepside/praziquantel (Profender®) in an MDR1-mutant Australian Shepherd dog: Case report. Front Vet Sci 6:296, 2019. Pubmed reference: 31555677. DOI: 10.3389/fvets.2019.00296. | |
Gagliardo, T., Gandini, G., Gallucci, A., Menchetti, M., Bianchi, E., Turba, M.E., Cauduro, A., Corlazzoli, D.S., Gianni, S., Baroni, M., Bernardini, M., Gentilini, F. : | |
ABCB1 c.-6-180T>G polymorphism and clinical risk factors in a multi-breed cohort of dogs with refractory idiopathic epilepsy. Vet J 253:105378, 2019. Pubmed reference: 31685133. DOI: 10.1016/j.tvjl.2019.105378. | |
Maués, T., El-Jaick, K.B., Costa, F.B., Freitas, P.V.S., Moreira, A.S., Castro, L., Ferreira, M.L.G., Ferreira, A.M.R. : | |
Could polymorphisms in ABCB1 gene represent a genetic risk factor for the development of mammary tumors in dogs? Vet J 248:58-63, 2019. Pubmed reference: 31113564. DOI: 10.1016/j.tvjl.2019.04.010. | |
Mealey, K.L., Martinez, S.E., Villarino, N.F., Court, M.H. : | |
Personalized medicine: going to the dogs? Hum Genet 138:467-481, 2019. Pubmed reference: 31032534. DOI: 10.1007/s00439-019-02020-w. | |
Silvestro, C.A., Soria, L.A., Conte, A., Marrube, G. : | |
Two methods for genotyping a 4-base deletion in the canine ABCB1 gene. J Vet Diagn Invest 31:889-892, 2019. Pubmed reference: 31711409. DOI: 10.1177/1040638719887374. | |
2018 | Merola, V.M., Eubig, P.A. : |
Toxicology of avermectins and milbemycins (Macrocyclic Lactones) and the role of p-glycoprotein in dogs and cats. Vet Clin North Am Small Anim Pract 48:991-1012, 2018. Pubmed reference: 30139545. DOI: 10.1016/j.cvsm.2018.07.002. | |
Myers, M.J., Martinez, M., Li, F., Howard, K., Yancy, H.F., Troutman, L., Sharkey, M., Myers, M.J., Martinez, M., Li, F., Howard, K., Yancy, H.F., Troutman, L., Sharkey, M. : | |
Impact of ABCB1 genotype in Collies on the pharmacokinetics of R- and S-fexofenadine. J Vet Pharmacol Ther 41:805-814, 2018. Pubmed reference: 30020547. DOI: 10.1111/jvp.12696. | |
2017 | Stiedl, C.P., Weber, K. : |
Fast and simple detection methods for the 4-base pair deletion of canine MDR1/ ABCB1 gene by PCR and isothermal amplification. J Vet Diagn Invest 29:176-180, 2017. Pubmed reference: 28061549. DOI: 10.1177/1040638716683213. | |
2016 | Donner, J., Kaukonen, M., Anderson, H., Möller, F., Kyöstilä, K., Sankari, S., Hytönen, M., Giger, U., Lohi, H. : |
Genetic panel screening of nearly 100 mutations reveals new insights into the breed distribution of risk variants for canine hereditary disorders. PLoS One 11:e0161005, 2016. Pubmed reference: 27525650. DOI: 10.1371/journal.pone.0161005. | |
Mizukami, K., Yabuki, A., Kohyama, M., Kushida, K., Rahman, M.M., Uddin, M.M., Sawa, M., Yamato, O. : | |
Molecular prevalence of multiple genetic disorders in Border collies in Japan and recommendations for genetic counselling. Vet J 214:21-3, 2016. Pubmed reference: 27387721. DOI: 10.1016/j.tvjl.2016.05.004. | |
2015 | Myers, M.J., Martinez, M., Li, H., Qiu, J., Troutman, L., Sharkey, M., Yancy, H.F. : |
Influence of ABCB1 Genotype in Collies on the Pharmacokinetics and Pharmacodynamics of Loperamide in a Dose-Escalation Study. Drug Metab Dispos 43:1392-407, 2015. Pubmed reference: 26153274. DOI: 10.1124/dmd.115.063735. | |
2013 | Mizukami, K., Yabuki, A., Chang, H.S., Uddin, M.M., Rahman, M.M., Kushida, K., Kohyama, M., Yamato, O. : |
High frequency of a single nucleotide substitution (c.-6-180T>G) of the canine MDR1/ABCB1 gene associated with phenobarbital-resistant idiopathic epilepsy in Border Collie dogs. Dis Markers 35:669-72, 2013. Pubmed reference: 24302812. DOI: 10.1155/2013/695918. | |
Tomiyasu, H., Goto-Koshino, Y., Fujino, Y., Ohno, K., Tsujimoto, H. : | |
Epigenetic regulation of the ABCB1 gene in drug-sensitive and drug-resistant lymphoid tumour cell lines obtained from canine patients. Vet J 199:103-109, 2013. Pubmed reference: 24332606. DOI: 10.1016/j.tvjl.2013.10.022. | |
2012 | Geyer, J., Janko, C. : |
Treatment of MDR1 mutant dogs with macrocyclic lactones. Curr Pharm Biotechnol 13:969-86, 2012. Pubmed reference: 22039792. DOI: 10.2174/138920112800399301. | |
Mizukami, K., Chang, H.S., Yabuki, A., Kawamichi, T., Hossain, M.A., Rahman, M.M., Uddin, M.M., Yamato, O. : | |
Rapid genotyping assays for the 4-base pair deletion of canine MDR1/ABCB1 gene and low frequency of the mutant allele in Border Collie dogs. J Vet Diagn Invest 24:127-34, 2012. Pubmed reference: 22362942. DOI: 10.1177/1040638711425591. | |
Parton, K., Wiffen, E.M., Haglund, N.D., Cave, N.J. : | |
Macrocyclic lactone toxicity due to abamectin in farm dogs without the ABCB1 gene mutation. N Z Vet J 60:194-7, 2012. Pubmed reference: 22329447. DOI: 10.1080/00480169.2011.642770. | |
Tappin, S.W., Goodfellow, M.R., Peters, I.R., Day, M.J., Hall, E.J., Mealey, K.L. : | |
Frequency of the mutant MDR1 allele in dogs in the UK. Vet Rec 171:72, 2012. Pubmed reference: 22735986. DOI: 10.1136/vr.100633. | |
2011 | Alves, L., Hülsmeyer, V., Jaggy, A., Fischer, A., Leeb, T., Drögemüller, M. : |
Polymorphisms in the ABCB1 gene in phenobarbital responsive and resistant idiopathic epileptic Border Collies. J Vet Intern Med 25:484-9, 2011. Pubmed reference: 21488961. DOI: 10.1111/j.1939-1676.2011.0718.x. | |
Gramer, I., Leidolf, R., Doring, B., Klintzsch, S., Kramer, EM., Yalcin, E., Petzinger, E., Geyer, J. : | |
Breed distribution of the nt230(del4) MDR1 mutation in dogs. Vet J 189:67-71, 2011. Pubmed reference: 20655253. DOI: 10.1016/j.tvjl.2010.06.012. | |
2010 | Han, JI., Son, HW., Park, SC., Na, KJ. : |
Novel insertion mutation of ABCB1 gene in an ivermectin-sensitive Border Collie. J Vet Sci 11:341-4, 2010. Pubmed reference: 21113104. | |
Hülsmeyer, V., Zimmermann, R., Brauer, C., Sauter-Louis, C., Fischer, A. : | |
Epilepsy in Border Collies: clinical manifestation, outcome, and mode of inheritance. J Vet Intern Med 24:171-8, 2010. Pubmed reference: 20391637. DOI: 10.1111/j.1939-1676.2009.0438.x. | |
Klintzsch, S., Meerkamp, K., Doring, B., Geyer, J. : | |
Detection of the nt230[del4] MDR1 mutation in dogs by a fluorogenic 5' nuclease TaqMan allelic discrimination method. Vet J 185:272-277, 2010. Pubmed reference: 19733104. DOI: 10.1016/j.tvjl.2009.07.018. | |
Sherman, JG., Paul, AJ., Firkins, LD. : | |
Evaluation of the safety of spinosad and milbemycin 5-oxime orally administered to Collies with the MDR1 gene mutation. Am J Vet Res 71:115-9, 2010. Pubmed reference: 20043790. DOI: 10.2460/ajvr.71.1.115. | |
2009 | Barbet, JL., Snook, T., Gay, JM., Mealey, KL. : |
ABCB1-1 Delta (MDR1-1 Delta) genotype is associated with adverse reactions in dogs treated with milbemycin oxime for generalized demodicosis. Vet Dermatol 20:111-4, 2009. Pubmed reference: 19171022. DOI: 10.1111/j.1365-3164.2008.00725.x. | |
Bissonnette, S., Paradis, M., Daneau, I., Silversides, DW. : | |
The ABCB1-1Delta mutation is not responsible for subchronic neurotoxicity seen in dogs of non-collie breeds following macrocyclic lactone treatment for generalized demodicosis. Vet Dermatol 20:60-6, 2009. Pubmed reference: 19152588. DOI: 10.1111/j.1365-3164.2008.00731.x. | |
2008 | Baars, C., Leeb, T., von Klopmann, T., Tipold, A., Potschka, H. : |
Allele-specific polymerase chain reaction diagnostic test for the functional MDR1 polymorphism in dogs. Veterinary Journal 177:394-7, 2008. Pubmed reference: 17644437. DOI: 10.1016/j.tvjl.2007.05.020. | |
Fecht, S., Wöhlke, A., Distl, O. : | |
Haplotype analysis of the MDR1 flanking region in the dog breed Elo. Berl Munch Tierarztl Wochenschr 121:211-5, 2008. Pubmed reference: 18557525. | |
Fecht, S., Distl, O. : | |
Review of prevalence, genetic aspects and adverse effects of the mdr1-1Delta mutation in dogs. Dtsch Tierarztl Wochenschr 115:212-9, 2008. Pubmed reference: 18605373. | |
Kitamura, Y., Koto, H., Matsuura, S., Kawabata, T., Tsuchiya, H., Kusuhara, H., Tsujimoto, H., Sugiyama, Y. : | |
Modest effect of impaired P-glycoprotein on the plasma concentrations of fexofenadine, quinidine, and loperamide following oral administration in collies. Drug Metab Dispos 36:807-10, 2008. Pubmed reference: 18299336. DOI: 10.1124/dmd.107.017624. | |
Mealey, K.L., Meurs, K.M. : | |
Breed distribution of the ABCB1-1Delta (multidrug sensitivity) polymorphism among dogs undergoing ABCB1 genotyping. J Am Vet Med Assoc 233:921-4, 2008. Pubmed reference: 18795852. DOI: 10.2460/javma.233.6.921. | |
Mealey, KL. : | |
Canine ABCB1 and macrocyclic lactones: heartworm prevention and pharmacogenetics. Vet Parasitol 158:215-22, 2008. Pubmed reference: 18922637. DOI: 10.1016/j.vetpar.2008.09.009. | |
2007 | Fecht, S., Wöhlke, A., Hamann, H., Distl, O. : |
Analysis of the canine mdr1-1Delta mutation in the dog breed Elo. J Vet Med A Physiol Pathol Clin Med 54:401-5, 2007. Pubmed reference: 17877579. DOI: 10.1111/j.1439-0442.2007.00966.x. | |
Geyer, J., Klintzsch, S., Meerkamp, K., Wöhlke, A., Distl, O., Moritz, A., Petzinger, E. : | |
Detection 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 30:482-5, 2007. Pubmed reference: 17803743. DOI: 10.1111/j.1365-2885.2007.00885.x. | |
Matsuura, S., Koto, H., Ide, K., Fujino, Y., Setoguchi-Mukai, A., Ohno, K., Tsujimoto, H. : | |
Induction of chemoresistance in a cultured canine cell line by retroviral transduction of the canine multidrug resistance 1 gene. Am J Vet Res 68:95-100, 2007. Pubmed reference: 17199425. DOI: 10.2460/ajvr.68.1.95. | |
2006 | Henik, RA., Kellum, HB., Bentjen, SA., Mealey, KL. : |
Digoxin and mexiletine sensitivity in a Collie with the MDR1 mutation. J Vet Intern Med 20:415-7, 2006. Pubmed reference: 16594604. | |
Mealey, K.L. : | |
Pharmacogenetics. Vet Clin North Am Small Anim Pract 36:961-73, v, 2006. Pubmed reference: 16984822. DOI: 10.1016/j.cvsm.2006.05.006. | |
2005 | Doering, B., Geyer, J., Godoy, J. R., Moritz, A., Petzinger, E. : |
Ivermectin neurotoxicity in dogs: A consequence of a mutation in the canine MDR 1 gene Naunyn-Schmiedeberg's Archives of Pharmacology 371:R2 only, 2005. | |
Geyer, J., Doring, B., Godoy, JR., Leidolf, R., Moritz, A., Petzinger, E. : | |
Frequency of the nt230 (del4) MDR1 mutation in Collies and related dog breeds in Germany. J Vet Pharmacol Ther 28:545-51, 2005. Pubmed reference: 16343287. DOI: 10.1111/j.1365-2885.2005.00692.x. | |
Hugnet, C. : | |
Veterinary pharmacogenetics: example of MDR1 mutation in Collie dogs Bulletin de l'Academie Veterinaire de France 158:67-70, 2005. | |
Kawabata, A., Momoi, Y., Inoue-Murayama, M., Iwasaki, T. : | |
Canine mdr1 gene mutation in Japan. J Vet Med Sci 67:1103-7, 2005. Pubmed reference: 16327220. | |
Mealey, KL., Munyard, KA., Bentjen, SA. : | |
Frequency of the mutant MDR1 allele associated with multidrug sensitivity in a sample of herding breed dogs living in Australia. Vet Parasitol 131:193-6, 2005. Pubmed reference: 15975717. DOI: 10.1016/j.vetpar.2005.05.004. | |
Turba, ME., Binns, M., Mellersh, C., Godoy, JR. : | |
Canine microsatellites associated with genes known to cause progressive retinal atrophy in dogs or retinitis pigmentosa in humans. Anim Genet 36:259-61, 2005. Pubmed reference: 15932411. DOI: 10.1111/j.1365-2052.2005.01271.x. | |
2004 | Hugnet, C., Bentjen, SA., Mealey, KL. : |
Frequency of the mutant MDR1 allele associated with multidrug sensitivity in a sample of collies from France. J Vet Pharmacol Ther 27:227-9, 2004. Pubmed reference: 15305851. DOI: 10.1111/j.1365-2885.2004.00585.x. | |
Neff, MW., Robertson, KR., Wong, AK., Safra, N., Broman, KW., Slatkin, M., Mealey, KL., Pedersen, NC. : | |
Breed distribution and history of canine mdr1-1Delta, a pharmacogenetic mutation that marks the emergence of breeds from the collie lineage. Proc Natl Acad Sci U S A 101:11725-30, 2004. Pubmed reference: 15289602. DOI: 10.1073/pnas.0402374101. | |
Sartor, LL., Bentjen, SA., Trepanier, L., Mealey, KL. : | |
Loperamide toxicity in a collie with the MDR1 mutation associated with ivermectin sensitivity. J Vet Intern Med 18:117-8, 2004. Pubmed reference: 14765742. | |
2003 | Mealey, K. L., Bentjen, S. A. : |
Sequence and structural analysis of the presumed downstream promoter of the canine mdr1 gene Veterinary and Comparative Oncology 1:30-35, 2003. | |
Mealey, KL., Northrup, NC., Bentjen, SA. : | |
Increased toxicity of P-glycoprotein-substrate chemotherapeutic agents in a dog with the MDR1 deletion mutation associated with ivermectin sensitivity. J Am Vet Med Assoc 223:1453-5, 1434, 2003. Pubmed reference: 14627096. | |
Nelson, OL., Carsten, E., Bentjen, SA., Mealey, KL. : | |
Ivermectin toxicity in an Australian Shepherd dog with the MDR1 mutation associated with ivermectin sensitivity in Collies. J Vet Intern Med 17:354-6, 2003. Pubmed reference: 12774979. | |
Roulet, A., Puel, O., Gesta, S., Lepage, JF., Drag, M., Soll, M., Alvinerie, M., Pineau, T. : | |
MDR1-deficient genotype in Collie dogs hypersensitive to the P-glycoprotein substrate ivermectin. Eur J Pharmacol 460:85-91, 2003. Pubmed reference: 12559367. | |
2002 | Mealey, KL., Bentjen, SA., Waiting, DK. : |
Frequency of the mutant MDR1 allele associated with ivermectin sensitivity in a sample population of collies from the northwestern United States. Am J Vet Res 63:479-81, 2002. Pubmed reference: 11939306. | |
2001 | Mealey, KL., Bentjen, SA., Gay, JM., Cantor, GH. : |
Ivermectin sensitivity in collies is associated with a deletion mutation of the mdr1 gene. Pharmacogenetics 11:727-33, 2001. Pubmed reference: 11692082. DOI: 10.1097/00008571-200111000-00012. | |
2000 | Mealey, K. L., Bentjen, S. A., Cantor, G. H. : |
Isolation and sequence of the promoter region of the canine multidrug resistance (P-glycoprotein) gene, MDR1 Journal of Veterinary Internal Medicine 14:359 only, 2000. | |
Paul, A.J., Tranquilli, W.J., Hutchens, D.E. : | |
Safety of moxidectin in avermectin-sensitive collies. Am J Vet Res 61:482-3, 2000. Pubmed reference: 10803640. DOI: 10.2460/ajvr.2000.61.482. | |
1996 | Schinkel, A.H., Wagenaar, E., Mol, C.A., van Deemter, L. : |
P-glycoprotein in the blood-brain barrier of mice influences the brain penetration and pharmacological activity of many drugs. J Clin Invest 97:2517-24, 1996. Pubmed reference: 8647944. DOI: 10.1172/JCI118699. | |
Steingold, S.S., Sharp, N.J., Fuller, F., Page, R.L. : | |
Semi-quantitative assessment of canine MDR1 mRNA using RT-PCR Proceedings of the American Association for Cancer Research Annual Meeting 37:310 only, 1996. | |
1995 | Hadrick, M.K., Bunch, S.E., Kornegay, J.N. : |
Ivermectin toxicosis in two Australian shepherds. J Am Vet Med Assoc 206:1147-50; discussion 1150-2, 1995. Pubmed reference: 7768734. | |
1991 | Fassler, P.E., Tranquilli, W.J., Paul, A.J., Soll, M.D., DiPietro, J.A., Todd, K.S. : |
Evaluation of the safety of ivermectin administered in a beef-based formulation to ivermectin-sensitive Collies. J Am Vet Med Assoc 199:457-60, 1991. Pubmed reference: 1917657. | |
1990 | Rohrer, S.P., Evans, D.V. : |
Binding characteristics of ivermectin in plasma from collie dogs. Vet Res Commun 14:157-65, 1990. Pubmed reference: 2345955. DOI: 10.1007/BF00346556. | |
1989 | Hsu, W.H., Wellborn, S.G., Schaffer, C.B. : |
The safety of ivermectin. Comp Contin Educat Vet 11:584-589, 1989. | |
Vaughn, D.M., Simpson, S.T., Blagburn, B.L., Whitmer, W.L., Heddens-Mysinger, R., Hendrix, C.M. : | |
Determination of homovanillic acid, 5-hydroxyindoleacetic acid and pressure in the cerebrospinal fluid of collie dogs following administration of ivermectin. Vet Res Commun 13:47-55, 1989. Pubmed reference: 2475964. DOI: 10.1007/BF00366852. | |
1987 | Paul, A.J., Tranquilli, W.J., Seward, R.L., Todd, K.S., DiPietro, J.A. : |
Clinical observations in collies given ivermectin orally. Am J Vet Res 48:684-5, 1987. Pubmed reference: 3592367. | |
1985 | Pulliam, J.D., Seward, R.L., Henry, R.T., Steinberg, S.A. : |
Investigating ivermectin toxicity in collies. Veterinary Medicine 7:33-40, 1985. | |
1984 | Campbell, W.C., Benz, G.W. : |
Ivermectin: a review of efficacy and safety. J Vet Pharmacol Ther 7:1-16, 1984. Pubmed reference: 6368862. DOI: 10.1111/j.1365-2885.1984.tb00872.x. |
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