Detection of heterozygous MDR1 nt230(del4) mutation in a mixed-breed dog: case report of possible doxorubicin toxicosis

Abstract:

P-glycoprotein (ABCB1), the product of the Multidrug Resistance Gene (MDR1) (ABCB1) gene, is the major multidrug transporter contributing to the barrier function of several tissues and organs, including the brain. A four base pair deletion mutation in MDR1 results in the absence of a functional form of ABCB1 and loss of its protective function. Severe intoxication with the ABCB1 substrate, such as with anticancer drugs, has been attributed to genetic lack of functional ABCB1. This mutation has been detected in more than 10 dog breeds as well as in mixed-breed dogs living in different countries. In Brazil, evaluation for this mutation is not as widely available and is rarely used by veterinarians, so drug intoxication may be underdiagnosed. This is the first report from Brazil of doxorubicin neurotoxicity in a mixed-breed dog with the MDR1 nt230(del4) mutation.

Keywords::

• canine
• toxicology
• cancer
• P-glycoprotein