B6;129-Nfkbib^tm1Bal/AlexJ

Stock number: 040984
Product name: IκBβ knock-out
Research areas: Cancer Research, Cell Biology Research, Immunology, Inflammation and Autoimmunity Research

Description

IκBβ knock-out (KO) mice carry a mutation that was generated by replacing exons 2-5 of the Nfkbib gene with a PGK-neomycin cassette, resulting in a null allele. These mice may be useful in studying the regulatory role of IκBβ on NF-κB activity in immune responses and inflammatory pathways.

Detailed description

Nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, beta (IκBβ) is a cellular protein that may function as a negative or positive regulator of NFκB signaling, depending on the context. It acts primarily as a positive regulator within the Rel-NFκB dimer generation module and is essential for the formation of RelA:RelA homodimers and, when bound to DNA, may protect them from attack from IκBα negative feedback. When deficient of other IκB proteins, IκBβ may compensate their loss and therefore function as an inhibitor. The NFκB pathway regulates transcription of genes associated with cell survival and proliferation, as well as immune and inflammatory responses. These IκBβ knock-out (KO) mice harbor a mutation generated by replacing Nfkbib exons 2 through 5 with a PGK-neomycin cassette resulting in complete loss of IκBβ.

Homozygous mice are viable and fertile with no overt phenotype in baseline conditions. IκBβ-deficient mice are reported to have hypo-inflammatory responses, reduced expression of TNF, and resistance to endotoxic shock and collagen-induced arthritis. These IκBβ KO mice may be useful when studying regulation of NFκB activity in immune and inflammatory pathways.

Development

The IκBβ knock-out (KO) targeting vector was designed to replace exons 2 through 5 of the nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, beta (Nfkbib) gene with a PGK-neomycin cassette. The construct was electroporated into 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺-derived CJ7 embryonic stem (ES) cells and correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric mice were then bred to C57BL/6J mice for at least 10 generations by the donating laboratory (see SNP note below). Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish a live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

In 2025, a 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. Six of the 43 markers throughout the genome were segregating with 129. Also, one of the 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed genetic background.

Allele

Symbol: Nfkbib^tm1Bal
Name: targeted mutation 1, David Baltimore
MGI accession ID: MGI:4822433
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Nfkbib
Marker name: nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, beta
Marker synonyms: IKappaBbeta; IkB; IKBB; TRIP9
Chromosome: 7
Strain of origin: 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Molecular note: Exons 2 through 5 were replaced with a neo cassette. The absence of protein expression was confirmed by western blot on extracts from E12.5-derived mouse embryonic fibroblasts.