Experimental Animal Division

B6.Cg-Nfkbiz<tm1.1Muta> (RBRC06410)

Courtesy of Takashi Maruyama, Ph.D.

IκB-ζ is one of the members of nuclear IκB family, which are characterized by the presence of ankyrin repeats. IκB-ζ interacts with NF-κB and regulates its activation to enhance expression of secondary response genes encoding inflammatory mediators such as IL-6 (A). Mice lacking IκB-ζ develop Sjögren’s syndrome (SS)-like dacryoadenitis, conjunctivitis, and periocular dermatitis [1, 2]. Muta, Maruyama, and their colleagues generated conditional Nfkbiz knockout mice in a C57BL/6 background, in which exons 5-7 of the gene were flanked by loxP sites (B). It has reported that exon 7 including transcriptional activation domain, and it plays a crucial role for transcription [3]. Similar inflammatory phenotype was observed in Nfkbiz floxed mice crossed with epithelial cell-specific Cre mice, but not in the hematopoietic cell-specific IκB-ζ knockout mice. Enhanced apoptosis in the epithelial cells was proven to be the cause of the SS-like phenotype [4]. The group also generated T cell-specific IκB-ζ knockout mice and revealed that TGF-β stimulation to naïve CD4+ T cells induced IκB-ζ expression, which resulted in decreased Ifng gene expression, and that IκB-ζ-deficient T_regs have a reduced immunoregulatory function. IκB-ζ is also critical for activation of natural killer cells, and Toll-like receptor-mediated class switch recombination in B cells [5-7]. Conditional knockout mice provide an opportunity to identify and characterize multiple functions of IκB-ζ.