Development and characterization of the MoN-Light BoNT assay to determine the toxicity of botulinum neurotoxin in motor neurons differentiated from CRISPR-modified induced pluripotent stem cells
Dissertation, Universität Potsdam, 2021
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Potsdam
2021
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Zusammenfassung: | Dissertation, Universität Potsdam, 2021 Botulinum neurotoxin (BoNT) is produced by the anaerobic bacterium Clostridium botulinum. It is one of the most potent toxins found in nature and can enter motor neurons (MN) to cleave proteins necessary for neurotransmission, resulting in flaccid paralysis. The toxin has applications in both traditional and esthetic medicine. Since BoNT activity varies between batches despite identical protein concentrations, the activity of each lot must be assessed. The gold standard method is the mouse lethality assay, in which mice are injected with a BoNT dilution series to determine the dose at which half of the animals suffer death from peripheral asphyxia. Ethical concerns surrounding the use of animals in toxicity testing necessitate the creation of alternative model systems to measure the potency of BoNT. Prerequisites of a successful model are that it is human specific; it monitors the complete toxic pathway of BoNT; and it is highly sensitive, at least in the range of the mouse lethality assay. One model system was developed by our ... |
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Beschreibung: | e, xviii, 265 Seiten Illustrationen, Diagramme |