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Generation of humanized mice for analysis of human dendritic cells


Saito, Y; Ellegast, J M; Manz, M G (2016). Generation of humanized mice for analysis of human dendritic cells. In: Segura, Elodie; Onai, Nobuyuki. Dendritic Cell Protocols. New York: Springer, 309-320.

Abstract

Transplantation of human CD34$^+$ hematopoietic stem and progenitor cells into severe immunocompromised newborn mice allows the development of a human hemato-lymphoid system (HHLS) including dendritic cells (DCs) in vivo. Therefore, it can be a powerful tool to study human DC subsets, residing in different lymphoid and nonlymphoid organs. We have recently generated novel mouse strains called human cytokine knock-in mice in which human versions of several cytokines are knocked into Rag2$^{-/-}$γC$^{-/-}$ strains. In addition, human SIRP$\alpha$, which is a critical factor to prevent donor cell to be eliminated by host macrophages, is expressed as transgene. These mice efficiently support human myeloid cell development and, indeed, allow the analysis of three major subsets of human DC lineages, plasmacytoid DCs and CD1c$^+$ and CD141$^+$ classical DCs. Moreover, these strains also support cytokine-mobilized peripheral blood CD34$^+$ cell engraftment and subsequent DC development. Here we describe our standard methods to characterize DCs developed in human cytokine knock-in mice.

Abstract

Transplantation of human CD34$^+$ hematopoietic stem and progenitor cells into severe immunocompromised newborn mice allows the development of a human hemato-lymphoid system (HHLS) including dendritic cells (DCs) in vivo. Therefore, it can be a powerful tool to study human DC subsets, residing in different lymphoid and nonlymphoid organs. We have recently generated novel mouse strains called human cytokine knock-in mice in which human versions of several cytokines are knocked into Rag2$^{-/-}$γC$^{-/-}$ strains. In addition, human SIRP$\alpha$, which is a critical factor to prevent donor cell to be eliminated by host macrophages, is expressed as transgene. These mice efficiently support human myeloid cell development and, indeed, allow the analysis of three major subsets of human DC lineages, plasmacytoid DCs and CD1c$^+$ and CD141$^+$ classical DCs. Moreover, these strains also support cytokine-mobilized peripheral blood CD34$^+$ cell engraftment and subsequent DC development. Here we describe our standard methods to characterize DCs developed in human cytokine knock-in mice.

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Additional indexing

Item Type:Book Section, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Hematology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2016
Deposited On:30 Jan 2017 14:21
Last Modified:02 Feb 2018 11:49
Publisher:Springer
Series Name:Methods in Molecular Biology
Number:1423
ISSN:1064-3745
ISBN:978-1-4939-3604-5
OA Status:Closed
Publisher DOI:https://doi.org/10.1007/978-1-4939-3606-9_22
PubMed ID:27142026

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