{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T09:27:29Z","timestamp":1775986049885,"version":"3.50.1"},"reference-count":37,"publisher":"American Veterinary Medical Association (AVMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2012,9]]},"abstract":"Abstract<\/jats:title>\nObjective<\/jats:bold>\u2014To develop in genetically engineered mice an alternative screening method for evaluation of P-glycoprotein substrate toxicosis in ivermectin-sensitive Collies.<\/jats:p>\nAnimals<\/jats:bold>\u201414 wild-type C57BL\/6J mice (controls) and 21 genetically engineered mice in which the abcb1a<\/jats:italic> and abcb1b<\/jats:italic> genes were disrupted and the mutated canine ABCB1<\/jats:italic> gene was inserted.<\/jats:p>\nProcedures<\/jats:bold>\u2014Mice were allocated to receive 10 mg of ivermectin\/kg via SC injection (n = 30) or a vehicle-only formulation of propylene glycol and glycerol formal (5). Each was observed for clinical signs of toxic effects from 0 to 7 hours following drug administration.<\/jats:p>\nResults<\/jats:bold>\u2014After ivermectin administration, considerable differences were observed in drug sensitivity between the 2 types of mice. The genetically engineered mice with the mutated canine ABCB1<\/jats:italic> gene had signs of severe sensitivity to ivermectin, characterized by progressive lethargy, ataxia, and tremors, whereas the wild-type control mice developed no remarkable effects related to the ivermectin.<\/jats:p>\nConclusions and Clinical Relevance<\/jats:bold>\u2014The ivermectin sensitivity modeled in the transgenic mice closely resembled the lethargy, stupor, disorientation, and loss of coordination observed in ivermectin-sensitive Collies with the ABCB1<\/jats:italic>\u20131\u0394 mutation. As such, the model has the potential to facilitate toxicity assessments of certain drugs for dogs that are P-glycoprotein substrates, and it may serve to reduce the use of dogs in avermectin derivative safety studies that are part of the new animal drug approval process.<\/jats:p>","DOI":"10.2460\/ajvr.73.9.1477","type":"journal-article","created":{"date-parts":[[2012,8,27]],"date-time":"2012-08-27T15:35:31Z","timestamp":1346081731000},"page":"1477-1484","source":"Crossref","is-referenced-by-count":11,"title":["Neurotoxic effects of ivermectin administration in genetically engineered mice with targeted insertion of the mutated canine ABCB1 gene"],"prefix":"10.2460","volume":"73","author":[{"given":"Krystyna L.","family":"Orzechowski","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marla D.","family":"Swain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin 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