A P2rx7 Passenger Mutation Affects the Vitality and Function of T cells in Congenic Mice
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A P2rx7 Passenger Mutation Affects the Vitality and Function of T cells in Congenic Mice. / Er-Lukowiak, Marco; Duan, Yinghui; Rassendren, Francois; Ulmann, Lauriane; Nicke, Annette; Ufer, Friederike; Friese, Manuel A; Koch-Nolte, Friedrich; Magnus, Tim; Rissiek, Björn.
in: ISCIENCE, Jahrgang 23, Nr. 12, 18.12.2020, S. 101870.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - A P2rx7 Passenger Mutation Affects the Vitality and Function of T cells in Congenic Mice
AU - Er-Lukowiak, Marco
AU - Duan, Yinghui
AU - Rassendren, Francois
AU - Ulmann, Lauriane
AU - Nicke, Annette
AU - Ufer, Friederike
AU - Friese, Manuel A
AU - Koch-Nolte, Friedrich
AU - Magnus, Tim
AU - Rissiek, Björn
N1 - © 2020 The Author(s).
PY - 2020/12/18
Y1 - 2020/12/18
N2 - Among laboratory mouse strains many genes are differentially expressed in the same cell population. As consequence, gene targeting in 129-derived embryonic stem cells (ESCs) and backcrossing the modified mice onto the C57BL/6 background can introduce passenger mutations in the close proximity of the targeted gene. Here, we demonstrate that several transgenic mice carry a P2rx7 passenger mutation that affects the function of T cells. By the example of P2rx4tm1Rass we demonstrate that P2X4ko T cells express higher levels of P2X7 and are more sensitive toward the P2X7 activators ATP and NAD+, rendering these cells more vulnerable toward NAD-induced cell death (NICD) compared with wild type (WT). The enhanced NICD sensitivity confounded functional assays e.g. cytokine production and cell migration. Our results need to be considered when working with P2rx4tm1Rass mice or other 129-based transgenic strains that target P2rx7 neighboring genes.
AB - Among laboratory mouse strains many genes are differentially expressed in the same cell population. As consequence, gene targeting in 129-derived embryonic stem cells (ESCs) and backcrossing the modified mice onto the C57BL/6 background can introduce passenger mutations in the close proximity of the targeted gene. Here, we demonstrate that several transgenic mice carry a P2rx7 passenger mutation that affects the function of T cells. By the example of P2rx4tm1Rass we demonstrate that P2X4ko T cells express higher levels of P2X7 and are more sensitive toward the P2X7 activators ATP and NAD+, rendering these cells more vulnerable toward NAD-induced cell death (NICD) compared with wild type (WT). The enhanced NICD sensitivity confounded functional assays e.g. cytokine production and cell migration. Our results need to be considered when working with P2rx4tm1Rass mice or other 129-based transgenic strains that target P2rx7 neighboring genes.
U2 - 10.1016/j.isci.2020.101870
DO - 10.1016/j.isci.2020.101870
M3 - SCORING: Journal article
C2 - 33336163
VL - 23
SP - 101870
JO - ISCIENCE
JF - ISCIENCE
SN - 2589-0042
IS - 12
ER -