0000000000189467
AUTHOR
Frauke Neff
Murine tissue factor disulfide mutation causes a bleeding phenotype with sex specific organ pathology and lethality.
Tissue factor is highly expressed in sub-endothelial tissue. The extracellular allosteric disulfide bond Cys186-Cys209 of human tissue factor shows high evolutionary conservation and in vitro evidence suggests that it significantly contributes to tissue factor procoagulant activity. To investigate the role of this allosteric disulfide bond in vivo, we generated a C213G mutant tissue factor mouse by replacing Cys213 of the corresponding disulfide Cys190-Cys213 in murine tissue factor. A bleeding phenotype was prominent in homozygous C213G tissue factor mice. Pre-natal lethality of 1/3rd of homozygous offspring was observed between E9.5 and E14.5 associated with placental hemorrhages. After b…
Naturally occurring autoantibodies interfere with β-amyloid metabolism and improve cognition in a transgenic mouse model of Alzheimer's disease 24 h after single treatment
There is evidence that naturally occurring antibodies directed against Aβ (nAbs-Aβ) have a role in Aβ-metabolism and Aβ-clearance. The presence of nAbs-Aβ leads to a reduction in amyloid fibrillation and thus a reduction in their toxicity. We investigated the effects of nAbs-Aβ in respect to oligomerization and used the Tg2576 transgenic mouse model in order to investigate the rapid effect with a single-dose (24 h) on oligomer breakdown and cytokine secretion along with immunohistochemical characterization of synaptic plasticity. nAbs-Aβ were able to reduce toxic oligomer concentration with an increase in Aβ-monomers. Cytokine secretion was significantly reduced. Synaptic plasticity was als…