Question

Dogs with which of the following mutation are predisposed to increased sensitivity to ivermectin and moxidectin ?

• A. PKFD
• B. ABCB1
• C. PIK3CA
• D. HUU

Hint:

Remember: "White feet, don't treat!"
Herding breeds with white socks (like Collies) are highly likely to carry the ABCB1 MDR1 mutation.
Always perform genetic testing or avoid macrocyclic lactones and loperamide in these breeds.

Answer 1

The Correct Option is B

Step 1: Understanding the Concept:
Certain dog breeds exhibit severe neurotoxicity when exposed to standard therapeutic doses of macrocyclic lactones (such as ivermectin and moxidectin).
This hypersensitivity is caused by a genetic mutation that impairs the blood-brain barrier.

Step 2: Detailed Explanation:
The sensitivity to macrocyclic lactones in dogs is caused by a mutation in the ABCB1 gene.
This gene was formerly known as the MDR1 (Multi-Drug Resistance 1) gene.
The ABCB1 gene encodes P-glycoprotein (P-gp), an ATP-dependent efflux pump located in the capillary endothelial cells of the blood-brain barrier.
In normal dogs, P-glycoprotein actively pumps potentially toxic compounds (including ivermectin, moxidectin, loperamide, and certain chemotherapeutic drugs) out of the brain parenchyma back into the capillary lumen.
Dogs homozygous for the ABCB1 mutation (often a 4-base pair deletion mutation) lack a functional P-glycoprotein pump.
Consequently, when these dogs receive macrocyclic lactones, the drugs cross the blood-brain barrier and accumulate to toxic levels in the central nervous system.
This leads to severe neurotoxicity, manifesting as hypersalivation, ataxia, tremors, blindness, coma, and death.
This mutation is highly prevalent in herding breeds, particularly Collies, Shetland Sheepdogs, and Australian Shepherds.
Let us review the other terms:
- PKFD stands for Pyruvate Kinase Deficiency, which causes hemolytic anemia.
- HUU stands for Hyperuricosuria, which predisposes dogs to uric acid bladder stones.

Step 3: Final Answer:
Dogs with the ABCB1 (MDR1) mutation are predisposed to increased sensitivity to ivermectin and moxidectin.