Conditional Knockout Mouse Models to Study the Roles of Individual NF-κB Transcription Factors in Lymphocytes.

Abstract

The NF-κB signal transduction pathway has crucial functions in cell growth, survival, and the development of lymphocytes and other immune cells. Upon activation of the pathway, five distinct NF-κB transcription factor subunits that occur as homodimers or heterodimers comprise the downstream mediators that transcribe NF-κB target genes. A major quest in NF-κB research is to understand the biology of the separate subunits. However, determining the functions of the individual subunits using constitutional knockout mice is often hampered by the marked cell type and/or developmental stage-specific activation of the NF-κB pathway. To overcome these problems, we and others have generated loxP-flanked alleles of the genes encoding the different NF-κB subunits that upon crossing to suitable Cre-expressing mouse lines can be conditionally deleted in the desired cell type or developmental stage. We here describe the basic characteristics of conditional NF-κB subunit alleles rel (encoding c-REL), rela (RELA), relb (RELB), and nfkb2 (NF-κB2) generated in our laboratory that are available to the research community through a repository, and provide basic methods to study the consequences of tissue-specific ablation of NF-κB transcription factors in lymphocytes.