Old English Sheepdog — Ivermectin sensitivity (hereditary; OMIA-verified breed predisposition)

--- license: permission_granted topic_id: companion_breed_health_old_english_sheepdog_ivermectin_sensitivity_dog category: companion-breed-health title: "Old English Sheepdog — Ivermectin sensitivity (hereditary; OMIA-verified breed predisposition)" lang: en source: "OMIA (Online Mendelian Inheritance in Animals, University of Sydney) breed-specific hereditary-disorder record, saved verbatim to source_file; C1 substring-verified. Pulled 2026-08-02 from local OMIA database dump." source_file: pdf-raw/breed-health/old_english_sheepdog_ivermectin_sensitivity_2759.txt date_parsed: 2026-08-02 tokens_estimated: 1085 verification: method: substring_match claims: 9 passed: 9 date: 2026-08-02 recovered: false path: companion-breed-health/companion_breed_health_old_english_sheepdog_ivermectin_sensitivity_dog/01_companion_breed_health_old_english_sheepdog_ivermectin_sensitivity_dog.md source_document: "OMIA — Online Mendelian Inheritance in Animals (University of Sydney)" citation: authority: "OMIA — Online Mendelian Inheritance in Animals (University of Sydney)" title: "Old English Sheepdog — Ivermectin sensitivity (hereditary; OMIA-verified breed predisposition)" url: "https://omia.org/OMIA001402/9615/" retrieved: "2026-08-02" ref: "OMIA breed-specific hereditary-disorder records (omia.org), derived from local OMIA database dump; dataset: https://doi.org/10.25910/2AMR-PV70" doc_type: "academic animal-genetics database (breed-specific disorder entries)" needs_review: false

Old English Sheepdog — Ivermectin sensitivity (hereditary; OMIA-verified breed predisposition)

Source: first-hand OMIA (University of Sydney) breed-specific hereditary-disorder record, saved verbatim to source_file; every claim below is a C1 byte-substring of it.

Claims

• Breed: Old English Sheepdog (Dog)
• Disorder: Ivermectin sensitivity
• Mode of inheritance: Autosomal incomplete dominant
• Summary: 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.
• Clin feat: 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]
• Defect: yes
• 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.-6-180Tgt;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.
• Gen test: Silvestro et al. (2019) developed two methods for genotyping the deletion variant.

Associated gene(s)

Derived from OMIA database dump (omia.xml, local); structured field, not verbatim prose. First-hand values below are verbatim substrings of the topic's pdf-raw/omia/<phene_id>.txt source file.

• Gene: MDR1 (Entrez Gene ID 26536055) — OMIA Phene_Gene / GeneSynonym
• OMIA molecular-genetics note: 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 prema…

Evidence (references)

Derived from OMIA database dump (omia.xml, local); structured field, not verbatim prose. First-hand values below are verbatim substrings of the topic's pdf-raw/omia/<phene_id>.txt source file.

• 2005. Canine microsatellites associated with genes known to cause progressive retinal atrophy in dogs or retinitis pigmentosa in humans. Anim Genet — PubMed:PMID15932411 | DOI:10.1111/j.1365-2052.2005.01271.x — OMIA Phene_Article / Article
• 2003. 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 — PubMed:PMID14627096 — OMIA Phene_Article / Article
• 2004. 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 — PubMed:PMID15289602 | DOI:10.1073/pnas.0402374101 — OMIA Phene_Article / Article
• 2004. Loperamide toxicity in a collie with the MDR1 mutation associated with ivermectin sensitivity. J Vet Intern Med — PubMed:PMID14765742 — OMIA Phene_Article / Article
• 2005. Frequency of the mutant MDR1 allele associated with multidrug sensitivity in a sample of herding breed dogs living in Australia. Vet Parasitol — PubMed:PMID15975717 | DOI:10.1016/j.vetpar.2005.05.004 — OMIA Phene_Article / Article
• 2005. Ivermectin neurotoxicity in dogs: A consequence of a mutation in the canine MDR 1 gene. Naunyn-Schmiedeberg's Archives of Pharmacology — OMIA Phene_Article / Article
• 2000. Isolation and sequence of the promoter region of the canine multidrug resistance (P-glycoprotein) gene, MDR1. Journal of Veterinary Internal Medicine — OMIA Phene_Article / Article
• 1996. Semi-quantitative assessment of canine MDR1 mRNA using RT-PCR. Proceedings of the American Association for Cancer Research Annual Meeting — OMIA Phene_Article / Article
• 2005. Veterinary pharmacogenetics: example of MDR1 mutation in Collie dogs. Bulletin de l'Academie Veterinaire de France — OMIA Phene_Article / Article
• 2003. Sequence and structural analysis of the presumed downstream promoter of the canine mdr1 gene. Veterinary and Comparative Oncology — OMIA Phene_Article / Article
• 2006. Digoxin and mexiletine sensitivity in a Collie with the MDR1 mutation. J Vet Intern Med — PubMed:PMID16594604 — OMIA Phene_Article / Article
• 2005. Frequency of the nt230 (del4) MDR1 mutation in Collies and related dog breeds in Germany. J Vet Pharmacol Ther — PubMed:PMID16343287 | DOI:10.1111/j.1365-2885.2005.00692.x — OMIA Phene_Article / Article
• (69 additional references in OMIA)

Comparative medicine (human OMIM)

Derived from OMIA database dump (omia.xml, local); structured field, not verbatim prose. First-hand values below are verbatim substrings of the topic's pdf-raw/omia/<phene_id>.txt source file.

• OMIM:171050 (type: gene) — OMIA Group_OMIM (via OMIA_ID)
• OMIM:120080 (type: trait) — OMIA Group_OMIM (via OMIA_ID)

verification_derived: method: derived_from_dataset source: "OMIA database dump (omia.xml, local); fields Gene/Variant/Article/OMIM" note: "Structured fields (gene, variant rsID/protein change, PubMed/DOI references, OMIM cross-link) extracted from OMIA dump and presented with first-hand values; not verbatim prose."