Double knockin mice show NF-KB trajectories in immune signaling and aging

Rahman SMT, Aqdas M, Martin EW, Ardori FT, Songkiatisak P, Oh KS, Uderhardt S, Yun S, Claybourne QC, Mcdevitt RA, Greco V, Germain RN, Tessarollo L, Sung MH (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Cell Reports Elsevier (Cell Press)

Book Volume: 41

Journal Issue: 8

DOI: 10.1016/j.celrep.2022.111682

Abstract

In vitro studies suggest that mapping the spatiotemporal complexity of nuclear factor KB (NF-KB) signaling is essential to understanding its function. The lack of tools to directly monitor NF-KB proteins in vivo has hin-dered such efforts. Here, we introduce reporter mice with the endogenous RelA (p65) or c-Rel labeled with distinct fluorescent proteins and a double knockin with both subunits labeled. Overcoming hurdles in simul-taneous live-cell imaging of RelA and c-Rel, we show that quantitative features of signaling reflect the identity of activating ligands, differ between primary and immortalized cells, and shift toward c-Rel in microglia from aged brains. RelA:c-Rel heterodimer is unexpectedly depleted in the nuclei of stimulated cells. Trajectories of subunit co-expression in immune lineages reveal a reduction at key cell maturation stages. These results demonstrate the power of these reporters in gaining deeper insights into NF-KB biology, with the spectral complementarity of the labeled NF-KB proteins enabling diverse applications.

Authors with CRIS profile

Stefan Uderhardt

Involved external institutions

Yale University US United States (USA) (US) National Institute on Aging (NIA) US United States (USA) (US) National Cancer Institute (NCI) US United States (USA) (US) US National Institutes of Health (NIH) US United States (USA) (US)

How to cite

APA:

Rahman, S.M.T., Aqdas, M., Martin, E.W., Ardori, F.T., Songkiatisak, P., Oh, K.-S.,... Sung, M.-H. (2022). Double knockin mice show NF-KB trajectories in immune signaling and aging. Cell Reports, 41(8). https://doi.org/10.1016/j.celrep.2022.111682

MLA:

Rahman, Shah Md Toufiqur, et al. "Double knockin mice show NF-KB trajectories in immune signaling and aging." Cell Reports 41.8 (2022).

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