Production of a p65 fl/fl /LysMCre mouse model with dysfunctional NF-κB signaling in bone marrow-derived macrophages

• Published in: Innate immunity (London, England) England), 2023-11, Vol.29 (8), p.171-185
• Main Authors: Korkaya, Ahmet K, Fischer, Jeffrey, Peppers, Anthony, Crosson, Sean M, Rayamajhi, Manira, Miao, Edward A, Baldwin, Jr, Albert S, Bradford, Jennifer W
• Format: Article
• Language: English
• Subjects: Animals; Disease Models, Animal; Female; Macrophages; Mice; NF-kappa B - metabolism; Signal Transduction; Transcription Factor RelA
• ISSN: 1753-4259; 1753-4267
• DOI: 10.1177/17534259231205993

Here, we describe the production and characterization of a novel p65 /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, p65 /LysMCre mice do not exhibit differences in naïve systemic immune profiles or colony forming units and time to death following infection as compared to controls. Additionally, p65 /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.