MDR1 (Multi-drug resistance 1)

MDR1 results in a higher risk of adverse reactions to P-glycoprotein substrates such as ivermectin and macrocyclic lactones. These substances are commonly found in flea and tick preventive products for cats and dogs. Clinical manifestations are neurological and include central nervous system depression, ataxia (impaired coordination of movements), tremors, salivation, vomiting, mydriasis (dilated pupils), respiratory disturbances and, in severe cases, coma or death.

In cats, MDR1 is caused by mutation c.1930_1931del in the ABCB1 gene, which encodes P-glycoprotein, a key transporter in drug degradation. The mutation results in the premature formation of a stop codon, the introduction of which can lead to abnormally truncated P-glycoprotein and impaired P-glycoprotein function.

The mode of inheritance of the mutation is autosomal recessive. This means that only individuals who inherit the mutated gene from both parents will develop the disease. Carriers of the mutated gene are clinically healthy but pass the mutation on to their offspring. In the case of a mating between two heterozygous individuals, theoretically 25% of the offspring will be completely healthy, 50% of the offspring will be carriers and 25% of the offspring will inherit the mutated gene from both parents and will therefore be affected by the disease.

The genetic test can clearly reveal the genotype of the animal and is a useful tool for breeders to prevent unintentional breeding of affected kittens.

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References:

Mealey, K.L., Burke, N.S. : Identification of a nonsense mutation in feline ABCB1. J Vet Pharmacol Ther 38:429-33, 2015. Pubmed reference: 25660379.