homeostasis/metabolism
• mutant mice are unable to synthesize GM3 ganglioside, a simple and widely distributed glycosphingolipid
• major brain gangliosides that are normally present in wild-type mice (GM1a, GD1b, and GT1b) are absent in the extract of mutant brain synaptosomes
• however, mutant mice express major ganglioside species that co-migrate with GM1b and GD1alpha gangliosides of the alpha-series
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• following i.v. injection of BoNT/CB-19 at an appropriate dose, mutant mice show prolonged survival time with the toxicity value reduced to 0.7% of that in wild-type controls
• in contrast, BoNT/003-9 and BoNT/1873 remain toxic and the i.p. LD50 dose estimated by survival time is ~70% of that in wild-type controls
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nervous system
• in vitro, Clostridium botulinum type C strain neurotoxin (BoNT/CB-19) fails to induce a concentration-dependent inhibition of glutamate release in mutant cerebellar granule cells in response to high K+ treatment, unlike in wild-type cells
• in contrast, BoNT/003-9 (a C/D mosaic toxin) and BoNT/1873 (type D toxin) still elicit an inhibitory effect on glutamate release, to the same extent as in wild-type granule cells
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mortality/aging
• following i.v. injection of BoNT/CB-19 at an appropriate dose, mutant mice show prolonged survival time with the toxicity value reduced to 0.7% of that in wild-type controls
• in contrast, BoNT/003-9 and BoNT/1873 remain toxic and the i.p. LD50 dose estimated by survival time is ~70% of that in wild-type controls
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