Summary:

The National Institute on Aging (NIA) and the National Cancer Institute (NCI) offer a suite of fluorescent NF-κB reporter mice (mEGFP- and mScarlet-tagged RelA and c-Rel knock-ins) that enable real-time visualization of endogenous NF-κB signaling dynamics in living cells and tissues. These research tools are available for licensing from The Jackson Laboratory for drug discovery, immunology, oncology, and inflammation research.

Description of Technology:

The nuclear factor kappa B (NF-κB) signaling pathway is a central regulator of inflammation, immunity, cell survival, and stress responses. Aberrant NF-κB signaling is associated with numerous diseases, including cancer, autoimmune disorders, and chronic inflammatory conditions. Existing NF-κB reporter models primarily rely on transcriptional or luciferase-based reporters. These only indirectly measure pathway activity and often lack the ability to visualize endogenous NF-κB dynamics in real time.

NIH investigators developed a suite of fluorescent NF-κB reporter mice (mEGFP-RelA knock-in,mScarlet-RelA knock-in, mEGFP-c-Rel knock-in, and mScarlet-c-Rel knock-in). They were created by inserting fluorescent protein tags into endogenous NF-κB transcription factor genes using CRISPR/Cas9 genome editing. These models express fluorescently tagged NF-κB proteins under native regulatory control, enabling direct visualization and quantification of endogenous NF-κB expression, localization, and nuclear translocation in living cells and tissues. The platform supports real-time studies of NF-κB signaling during normal physiology, inflammation, aging, immune responses, and disease.

The Jackson Laboratory Stock #s:

• Stock No. 041814 – mEGFP-RelA knock-in
• Stock No. 041815 – mScarlet-RelA knock-in
• Stock No. 041816 – mEGFP-c-Rel knock-in
• Stock No. 041817 – mScarlet-c-Rel knock-in

Potential Commercial Applications:

• Drug discovery and screening of NF-κB pathway inhibitors and activators
• Preclinical testing of anti-inflammatory, immunology, and oncology therapeutics
• Live-cell and intravital imaging of RelA/c-Rel signaling dynamics
• Studies of inflammatory diseases, cancer, and aging
• Target validation and biomarker discovery

Competitive Advantages:

• Direct visualization of endogenous RelA/c-Rel dynamics
• mScarlet fluorescence signal suitable for deep-tissue imaging
• Native expression from the endogenous Rela locus or the endogenous Rel locus
• Eliminates the need for substrate administration required by luciferase reporters
• Compatible with multiplex imaging, flow cytometry, microscopy, fluorescence correlation spectroscopy, and live-cell imaging
• Tissue-specific or conditional knockout of Rela or Rel by crossing to a Cre mouse line