Mice homozygous for the NIK-deltaT3 allele are viable and fertile, with a loxP-flanked Neo-STOP cassette preventing transcription of the downstream bicistronic sequences (NIKdeltaT3 [a constitutively active form of the mouse NF-kappaB inducing kinase] and EGFP). When bred to mice that express Cre recombinase, offspring will have the STOP cassette deleted and subsequent expression of the NIKdeltaT3 molecule and EGFP fluorescence in the cre-expressing cells. Expression of NIK-deltaT3 leads to uncoupling NIK from tumor necrosis factor receptor-associated factor 3 (TRAF3)-mediated control causing maximal p100 processing and dramatic hyperplasia of B cell-activating factor
of the TNF family receptor (BAFF-R)-independent B cells. BAFF-R binding is required to sustain the NIK p100 subunit processing needed for B cell survival, as implicated in human multiple myeloma.
Of note, breeding these mice to an FLP-expressing strain will result in removal of the frt-flanked IRES-EGFP cassette.
When bred to a strain expressing Cre recombinase throughout B lymphocyte development and differentiation (see Stock No. 006785 for example), this mutant mouse strain exhibits increased B cell numbers.
