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IVERMECTIN neurotoxicosis in rough collies is caused by a frame-shift mutation within the multidrug resistance (MDR1) gene (also referred to as ABCB1), leading to the production of incomplete P-glycoprotein (Mealey and others 2001). P-glycoprotein is an ATP-dependent drug transporter, and the mutation leads to toxicity caused by ivermectin and a wide variety of P-glycoprotein substrates, including vincristine and doxorubicin (Mealey and others 2003), loperamide (Sartor and others 2004), moxidectin (Geyer and others 2005a), digoxin and mexiletine (Henik and others 2006). Although most dogs with adverse drug reactions are homozygous for the MDR1 mutation, heterozygous animals can also be affected, and dose reductions for many drugs are suggested for both heterozygotes and homozygotes (Martinez and others 2008).
The prevalence of rough collies with heterozygous MDR1 mutations is high, with the frequency of affected dogs varying slightly between geographical locations with allelic frequencies of 64 per cent reported in France (Hugnet and others 2004), 59 per cent in Germany (Gramer and others 2011), 58 per cent in Japan (Kawabata and others 2005) and 56per cent in the USA (Mealey and Meurs 2008). The MDR1 mutation documented in rough collies has since been discovered within several other related breeds including Australian shepherd dogs, old English sheepdogs, Shetland sheepdogs (Neff and others 2004), Border collies (Geyer and others 2005b), and more recently, German shepherd dogs, white Swiss shepherd dogs, miniature Australian shepherd dogs and …