Production of a p65fl/fl/LysMCre mouse model with dysfunctional NF-kappaB signaling in bone marrow-derived macrophages

Date

Authors

Bradford, jennifer W
Korkaya, Ahment K
Fischer, Jeffrey
Peppers, Anthony
Crosson, Sean
Rayamajhi, Manira
Miao, Edward A
Baldwin Jr, Albert S

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Journal ISSN

Volume Title

Publisher

Sage Journals

Abstract

Here, we describe the production and characterization of a novel p65fl/fl/LysMCre mouse model, which lacks canonical nuclear factor-kappaB member RelA/p65 (indicated as p65 hereafter) in bone marrow-derived macrophages. Cultured bone marrow-derived macrophages that lack p65 protein reveal NF-κB signaling deficiencies, a reduction in phagocytic ability, and reduced ability to produce nitrites. Despite abnormal bone marrow-derived macrophage function, p65fl/fl/LysMCre mice do not exhibit differences in naïve systemic immune profiles or colony forming units and time to death following Salmonella infection as compared to controls. Additionally, p65fl/fl/LysMCre mice, especially females, display splenomegaly, but no other obvious physical or behavioral differences as compared to control animals. As bone marrow-derived macrophages from this transgenic model are almost completely devoid of canonical nuclear factor-kappaB pathway member p65, this model has the potential for being very useful in investigating bone marrow-derived macrophage NF-kappaB signaling in diverse biological and biomedical studies.

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Keywords

Animal model, bone marrow-derived macrophage, cytokine, innate immunity, nuclear factor-kappaB

Citation

DOI