ABCB1 gene (=MDR1 gene-multi-Drug-Resistance)-Homozygous or heterozygous 4 base pair deletions in exon 4: PCR and sequencing.
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ABCB1 gene (ATP-Binding Cassette protein subfamily B member 1) (MDR1-Multidrug resistance), located on canine chromosome 14, codifies for P-glycoprotein (P-gp) transporter (170 Kda membrane protein). This protein acts as a cellular efflux pump to control the intracellular concentration of substances being an effective cellular protector against toxic substances. A delection of 4-bp (del4) in the gene lead to a stop codons that cause premature termination of P-glycoprotein 1 (P-gp) synthesis. ABCB1 gene polymorphism is associated with increased susceptibility to adverse reactions and hypothalamic–pituitary–adrenal axis suppression for various commonly used veterinary drugs, resulting in buildup of these drugs in the brain and hence severe neurotoxicity. This non-functional transporter promotes toxic reaction after administration of ivermectin mainly in homozygous mutant -MDR1 (+/+)-, and unpredictable in heterozygous mutant -MDR1 (+/-)-. The toxic reaction can be promoted by other drugs (milbemycin, selamectin, moxidectin, loperamide, acepromazine, butorphanol, vincristine, vinblastine, doxorubicin, paclitaxel, apomorphile, emodepside, …).