The only one strain for study of NF-kB/RelA subunit in vivo
|(1)Body weight change:
There is the significant growth retardation in TNF-kB mice (genotype; TNF-/- RelA-/-). The body weight of TNF-kB mice at 3 weeks after birth is significantly low, as shown in figure-1.
|(2)TNF sensitivity of macrophages:
TNF-kB mice (genotype: TNF-/- RelA-/-)-derived macrophages are highly sensitive to TNF, as shown in figure-2
TNF, tumor necrosis factor is a multifunction proinflammatory cytokine. RelA, v-rel reticuloendotheliosis viral oncogene homolog A (Avian) is one of NF-κB family relating to the development of lymphocytes. Mice lacking only Rela gene die between days 14 and 15 of embryogenesis because of liver cell apoptosis by endogenous TNF cytotoxicity. Meanwhile, homozyogous Tnf/Rela double-deficient mice are viable and have normal liver at birth. This strain is only one which is useful for studies of functions of Rela in vivo. Neomycin casettes were inserted into the nucleotides 3704-5364 of the Tnf gene and the downstream of the translation initiation codon of the Rela gene, respectively. Homozygous TNF-kB deficient mice are born with normal livers, but die within 5 weeks after birth with growth retardation as shown in figure-1. And the macrophages derived from this strain are highly sensitive to TNF, as shown in figure-2.
|Depositor||:||Takahiro DOI, RIKEN BRC|
|References||:||1.||Doi TS et al. NF-kappa B RelA-deficient lymphocytes: normal development of T cells and B cells, impaired production of IgA and IgG1 and reduced proliferative responses. J Exp Med. 1997 Mar 3;185(5):953-961.|
|2.||Marino MW et al. Characterization of tumor necrosis factor-deficient mice. Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8093-8098.|
|3.||Doi TS et al. Absence of tumor necrosis factor rescues RelA-deficient mice from embryonic lethality. Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2994-2999.|