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Publication : Optimal route of diphtheria toxin administration to eliminate native nephron progenitor cells in vivo for kidney regeneration.

First Author  Fukunaga S Year  2018
Journal  Biochem Biophys Res Commun Volume  496
Issue  4 Pages  1176-1182
PubMed ID  29408475 Mgi Jnum  J:272273
Mgi Id  MGI:6280254 Doi  10.1016/j.bbrc.2018.01.166
Citation  Fukunaga S, et al. (2018) Optimal route of diphtheria toxin administration to eliminate native nephron progenitor cells in vivo for kidney regeneration. Biochem Biophys Res Commun 496(4):1176-1182
abstractText  To address the lack of organs for transplantation, we previously developed a method for organ regeneration in which nephron progenitor cell (NPC) replacement is performed via the diphtheria toxin receptor (DTR) system. In transgenic mice with NPC-specific expression of DTR, NPCs were eliminated by DT and replaced with NPCs lacking the DTR with the ability to differentiate into nephrons. However, this method has only been verified in vitro. For applications to natural models, such as animal fetuses, it is necessary to determine the optimal administration route and dose of DT. In this study, two DT administration routes (intra-peritoneal and intra-amniotic injection) were evaluated in fetal mice. The fetus was delivered by caesarean section at E18.5, and the fetal mouse kidney and RNA expression were evaluated. Additionally, the effect of the DT dose (25, 5, 0.5, and 0.05 ng/fetus-body) was studied. Intra-amniotic injection of DT led to a reduction in kidney volume, loss of glomeruli, and decreased differentiation marker expression. The intra-peritoneal route was not sufficient for NPC elimination. By establishing that intra-amniotic injection is the optimal administration route for DT, these results will facilitate studies of kidney regeneration in vivo. In addition, this method might be useful for analysis of kidney development at various time points by deleting NPCs during development.
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