Which dog breeds are sensitive to ivermectin and why (mdr1 mutation)?
Executive summary
The MDR1/ABCB1 deletion (nt230(del4)) is the genetic reason many herding breeds—most notably Collies and Australian Shepherds—are hypersensitive to ivermectin and related drugs because the mutation disrupts P‑glycoprotein drug export at the blood‑brain barrier [1] [2] [3]. Homozygous dogs (two copies) are at greatest risk of neurological toxicity at doses far lower than tolerant breeds, though most FDA‑approved monthly heartworm doses are reported safe even in MDR1 dogs [2] [4] [5].
1. How the mutation causes ivermectin sensitivity — a pharmacology short story
Researchers linked a 4‑base‑pair deletion in the canine MDR1 (ABCB1) gene to ivermectin sensitivity; the gene encodes P‑glycoprotein (P‑gp), a transporter that pumps many drugs out of the brain, so the defective protein allows ivermectin and other P‑gp substrates to accumulate in the central nervous system and produce tremors, ataxia, seizures or coma [1] [2] [6].
2. Which breeds are most commonly affected — who to worry about
The variant was first identified in Collies but has been documented across many herding and related breeds: Collies, Australian Shepherds, Shetland Sheepdogs, Border Collies, Old English Sheepdogs, English Shepherds, German Shepherds, White Swiss Shepherds, McNabs, Wällers, Longhaired Whippets and others — and it appears in mixed‑breed dogs with herding ancestry [7] [8] [3].
3. Genotype matters — one copy versus two copies
Dogs homozygous for the MDR1 deletion (two mutant alleles) reliably show multidrug sensitivity and high risk of severe ivermectin neurotoxicity; heterozygous dogs (one mutant allele) may also show sensitivity at higher doses but typically less severely [7] [9] [2].
4. Doses and real‑world risk — monthly heartworm prevention vs. high‑dose exposures
Multiple sources report that the low, FDA‑approved monthly heartworm ivermectin doses are generally safe even in MDR1‑mutant dogs, while high or accidental exposures (for example, using livestock doses or deworming horses’ products) can produce life‑threatening CNS signs in affected animals [4] [3] [10].
5. Beyond ivermectin — a wider drug list and clinical implications
The MDR1 defect raises risk not only for macrocyclic lactones (ivermectin, milbemycin, selamectin, moxidectin) but for many other veterinary and human drugs that are P‑gp substrates or affected by P‑gp interactions — examples cited include loperamide, acepromazine, certain anticancer drugs (vincristine, doxorubicin), digoxin, and some antiemetics and antibiotics; clinical toxicity depends on drug, dose, and genotype [8] [11] [7].
6. Testing, management and competing perspectives
Veterinary sources uniformly recommend genetic testing to identify MDR1 status before giving high‑risk drugs; several sources stress that elimination of dogs with the mutation from breeding programs isn’t universally recommended because heterozygotes can be managed and the mutation is widespread [3] [11] [7]. Some consumer‑oriented guides emphasize high carrier rates (e.g., “up to 75% in some Collie populations” cited in one article) and urge routine testing for many mixed breeds [12], while core veterinary literature frames risk more narrowly around dose‑dependent toxicities and the role of genotype [2] [4].
7. Practical takeaways for owners and clinicians
If you own or treat herding breeds or mixed dogs with herding ancestry, test for MDR1 before using non‑routine antiparasitics or drugs known to be P‑gp substrates; use labeled heartworm products as directed because those doses are repeatedly reported safe for MDR1 dogs, avoid off‑label high‑dose ivermectin or livestock formulations, and anticipate more severe signs if a homozygous dog is exposed [5] [4] [2].
8. Limits of the current reporting and remaining questions
Available sources establish the deletion mutation and list affected breeds and drugs, but they do not provide uniform carrier‑frequency numbers for every breed or precise dose‑thresholds for toxicity in every clinical scenario; breed prevalence figures vary by study and geography, and sources differ slightly on how commonly heterozygotes display symptoms [8] [3] [12].
Sources cited above document the molecular cause, breed distribution, dose dependence and clinical guidance: Mealey et al. and follow‑up reviews linking the nt230(del4) MDR1 deletion to ivermectin sensitivity [1] [2], veterinary hospital and university advisories that low heartworm doses are safe while high doses are risky [4] [3], and lab/test and breed‑distribution reports that expand the list of affected breeds [7] [8].