In vivo modulation of gene expression by lentiviral transduction in "human immune system" Rag2-/- gamma c -/- mice

Methods in Molecular Biology
Anja U van LentN Legrand

Abstract

Over the last two decades, several humanized mouse models have been used to experimentally analyze the function and development of the human immune system. Recent advances have lead to the establishment of new murine-human chimeric models with improved characteristics, both in terms of human engraftment efficiency and in situ multilineage human hematopoietic development. We describe here the use of newborn BALB/c Rag2(-/-)gamma(c) (-/-) mice as recipients of human hematopoietic progenitor cells to produce "human immune system" (HIS) (BALB-Rag/gamma) mice, using human fetal liver progenitors. The two major subsets of the human dendritic cell lineage, namely, BDCA2(+)CD11c(-) plasmacytoid dendritic cells and BDCA2(-)CD11c(+) conventional dendritic cells, can be found in HIS (BALB-Rag/gamma) mice. In order to manipulate the expression of genes of interest, the human hematopoietic progenitor cells can be genetically engineered ex vivo by lentiviral transduction before performing xenograft transplantation. Using this mouse model, the human immune system can be assessed for both fundamental and pre-clinical purposes.

Citations

Jul 27, 2011·Proceedings of the National Academy of Sciences of the United States of America·Nicolas LegrandHergen Spits
Jun 1, 2012·The Journal of General Virology·Nicolas LegrandMireille Centlivre
Oct 15, 2013·Nature Medicine·Carsten LinnemannTon N M Schumacher
Aug 24, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Evert-Jan WilsJan J Cornelissen
Feb 1, 2012·Médecine sciences : M/S·Anne CachatMadeleine Duc Dodon

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