摘要：SummaryAmong 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 aP2rx7passenger mutation that affects the function of T cells. By the example of P2rx4tm1Rasswe 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 P2rx4tm1Rassmice or other 129-based transgenic strains that targetP2rx7neighboring genes.Graphical AbstractDisplay OmittedHighlights•T cells from 129 mice express higher level of P2X7 compared with T cells from B6 mice•P2rx4tm1RassT cells express high level of P2X7 due to aP2rx7passenger mutation•P2rx4tm1RassT cells are highly susceptible to NAD-induced cell death (NICD)•NICD susceptibility of P2rx4tm1RassT cells confounds the outcome of functional assaysGenetics; Immunology
