Let's talk about MDR1 in Australian Shepherds.

The Multi-Drug Resistance Gene (MDR1) encodes DNA for a protein that helps protect the brain by removing potentially harmful substances. In some breeds, a mutation in the MDR1 gene leads to sensitivity to several common drugs. The protein wrongly identifies these drugs as safe and does not expel them. If dogs with MDR1 mutations receive these drugs, the consequences can be fatal.

Dogs with this mutation have a malfunction in the P-glycoprotein, which normally removes certain drugs from the brain. The faulty protein prevents the dog from eliminating these drugs, causing a toxic buildup. This accumulation results in neurological issues such as seizures, ataxia, or even death.

Dogs that are homozygous for the MDR1 gene (having two copies of the mutated gene) consistently show sensitivity to Ivermectin and related drugs. These dogs will always pass one mutated gene copy to all their offspring.

Dogs that are heterozygous (with one mutated gene copy) can still have adverse reactions to these drugs at higher doses. There is a 50% chance that a dog with one mutation copy will transmit it to any offspring. When breeding carriers, it's crucial to understand there's a 25% chance per puppy of being homozygous for the MDR1 gene, resulting in lethal “allergies” to the drugs listed below.

Numerous drugs have been reported to cause issues. Here is a list of some of these drugs:

• Ivermectin (in heartworm medications)

• Loperamide

  • (Imodium, an over-the-counter antidiarrheal)

• Anti-cancer agents:

  • Doxorubicin

  • Vincristine

  • Vinblastine

• Cyclosporin (immunosuppressant)

• Digoxin (cardiac drug)

• Acepromazine (sedative)

• Butorphanol ("Bute" for pain management)

The following drugs might also pose problems:

• Ondansetron

• Domperidone

• Paclitaxel

• Mitoxantrone

• Etoposide

• Rifampicin

• Quinidine

• Morphine