{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:14:36Z","timestamp":1787030076165,"version":"build-2736575974"},"reference-count":146,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,12,7]],"date-time":"2019-12-07T00:00:00Z","timestamp":1575676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI139306"],"award-info":[{"award-number":["R01AI139306"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Botulinum Neurotoxins (BoNTs) are a large protein family that includes the most potent neurotoxins known to humankind. BoNTs delivered locally in humans at low doses are widely used pharmaceuticals. Reliable and quantitative detection of BoNTs is of paramount importance for the clinical diagnosis of botulism, basic research, drug development, potency determination, and detection in clinical, environmental, and food samples. Ideally, a definitive assay for BoNT should reflect the activity of each of the four steps in nerve intoxication. The in vivo mouse bioassay (MBA) is the \u2018gold standard\u2019 for the detection of BoNTs. The MBA is sensitive, robust, semi-quantitative, and reliable within its sensitivity limits. Potential drawbacks with the MBA include assay-to-assay potency variations, especially between laboratories, and false positives or negatives. These limitations can be largely avoided by careful planning and performance. Another detection method that has gained importance in recent years for research and potency determination of pharmaceutical BoNTs is cell-based assays, as these assays can be highly sensitive, quantitative, human-specific, and detect fully functional holotoxins at physiologically relevant concentrations. A myriad of other in vitro BoNT detection methods exist. This review focuses on critical factors and assay limitations of the mouse bioassay and cell-based assays for BoNT detection.<\/jats:p>","DOI":"10.3390\/toxins11120713","type":"journal-article","created":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T05:54:51Z","timestamp":1575870891000},"page":"713","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Critical Analysis of Neuronal Cell and the Mouse Bioassay for Detection of Botulinum Neurotoxins"],"prefix":"10.3390","volume":"11","author":[{"given":"Sabine","family":"Pellett","sequence":"first","affiliation":[{"name":"Department of Bacteriology, University of Wisconsin-Madison, 1550 Linden Dr, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William H.","family":"Tepp","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, University of Wisconsin-Madison, 1550 Linden Dr, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, University of Wisconsin-Madison, 1550 Linden Dr, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1007\/s00415-018-8759-1","article-title":"Defining spasticity: A new approach considering current movement disorders terminology and botulinum toxin therapy","volume":"265","author":"Dressler","year":"2018","journal-title":"J. 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