Diphtheria toxin mutant selectively kills cerebellar Purkinje neurons.
AUTOR(ES)
Riedel, C J
RESUMO
CRM107 (crossreacting material 107), a double point mutant of diphtheria toxin that lacks receptor-binding activity, specifically kills cerebellar Purkinje cells in vivo. After injection into guinea pig cerebrospinal fluid, CRM107 (0.9 micrograms) and CRM107-monoclonal antibody conjugates (10 micrograms) kill up to 90% of the total Purkinje cell population with no detectable toxicity to other neurons. Animals exhibit ataxia, tremor, and abnormalities of posture and tone. Native diphtheria toxin, ricin, and ricin A chain do not cause ataxia and do not reduce the Purkinje cell population after intrathecal injection into guinea pigs at toxic or maximally tolerated doses. However, in rats, which will tolerate higher doses of diphtheria toxin than guinea pigs, Purkinje cells can be killed by both CRM107 and diphtheria toxin. A truncated mutant of diphtheria toxin, called CRM45, can also cause Purkinje cell killing but has additional toxicity not seen with CRM107. Animals treated with intrathecal CRM107 or CRM107 linked to antibodies may serve as models for Purkinje cell loss in a broad spectrum of human diseases and may be used to further study cerebellar physiology. Understanding the basis for the Purkinje cell sensitivity to CRM107 may illuminate other causes of Purkinje cell loss.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=54259Documentos Relacionados
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