Multi Drug resistance (MDR1)

This mutation causes a frame shift and formation of a stop codon during P-glycoprotein synthesis.
P-glykoprotein, an ATP-dependent transporter of various substrates, is contained in cells lining the
blood vessels in the brain. In P-glycoprotein defective animals, administering of ivermectin or
similar drug can lead to elevated levels of drug in the CNS, resulting in potentially lethal neurotoxic
reaction. These drugs include, but are not limited to: Acepromazine, Butorphanol, Doramectin,
Doxorubicin, Ivermectin, Loperamide, Milbemycin, Moxidectin, Selamectin, Vinblastine, Vincristine.
Mutation that causes MDR1 related drug hypersensitivity is inherited as an autosomal recessive
trait. That means the defect affects dogs with P/P (positive / positive) genotype only. The dogs
with N/P (negative / positive) genotype are considered carriers of the deletion (heterozygotes).
The dogs with N/N genotype are not endangered with MDR1 related drug hypersenzitivity.
Multiple drug hypersensitivity based on MDR1 gene mutation was proved in following breeds:
Rough Collie, Smooth Collie, Shetland Sheepdog, Australian Sheepdog, White Swiss Shepherd Dog,
Wäller, Bobtail, Border Collie and others.

 

Autosomal recessive heredity

Parent 1 genotype

Parent 2 genotype

Normal (+/+)

Carrier (+/-)

Affected (-/-)

Normal (+/+)

All Normal

½ Normal
½ Carrier

All Carriers

Carrier (+/-)

½ Normal
½ Carriers

¼ Normal
½ Carriers
¼ Affected

½ Carriers
½ Affected

Affected (-/-)

All Carriers

½ Carriers
½ Affected

All Affected

 

Genetic DNA testing available