Mice homozygous for the Nfkb1tm1Bal knock-out mutation exhibit defective B cell responses, defective responses to infection, and also defects in basal and specific antibody production. These mice may be useful in studies of inflammation and immune responses and signal transduction.
Menno de Winther, Academic Medical Center
Mice homozygous for the Nfkb1tm1Bal targeted mutation are viable and fertile. Homozygous mutant mice exhibit defective B cell responses, defective responses to infection, and also defects in basal and specific antibody production. These mice may be useful in studies of inflammation and immune responses and signal transduction.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
A targeting vector containing the PGK-neo resistance gene in opposite transcriptional orientation was designed to disrupt exon 6 of the endogenous gene. The construct was electroporated into 129P2/OlaHsd-derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts amd the resulting chimeric mice were crossed with C57BL/6J mice. Heterozygous mice were bred to create homozygous mice on a mixed B6;129P2 background prior to arrival at The Jackson Laboratory. Dr. Menno de Winther of Maastricht University, The Netherlands obtained JR#002849 from The Jackson Laboratory and backcrossed them to C57BL/6JIco for 12 generations.
|Allele Name||targeted mutation 1, David Baltimore|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||NF-kappaBtm1Bal; Nfkappab1-; NF-kappaB1 KO; NF-kappaB1-; NFkappaB10; Nfkb1-; p105-; p50-; p50KO|
|Gene Symbol and Name||Nfkb1, nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105|
|Strain of Origin||129P2/OlaHsd|
|General Note|| |
Effect of reconstitution with Nfkb1tm1Bal homozygous hematopoietic cells on atherogenesis in atherosclerosis prone mice
To assess the role of NFKB1 in atherogenesis, mice homozygous for a mutation of the low density lipoprotein receptor (Ldlrtm1Her) were lethally irradiated and transplanted with bone marrow from Nfkb1tm1Bal homozygous mice and 4 weeks later placed on a high-fat diet for 10 weeks. Aortic root lesion area of mice with NFKB1-deficient hematopoietic cells was 41% smaller than in control mice. Whereas control lesions contained primarily large foam cells, lesions of mice reconstituted with NFKB1-deficient bone marrow contained large numbers of small, inflammatory cells and very few foam cells. 3-fold as many cells attached to the lesion cap in transplanted mice. Most cells in control lesions were macrophages, while in transplanted mice there was a preponderance of T and B lymphocytes.
Macrophages induced to differentiate in culture from NFKB1-deficient bone marrow exhibited differences compared to control macrophages in the secretion patterns of several cytokines following lipopolysaccharide (LPS) stimulation. Whereas control macrophages expressed high levels of scavenger receptor class A (SR-A) in response to LPS, this response was greatly attenuated in mice with NFKB1-deficient hematopoietic systems; uptake of oxidized low density lipoprotein (oxLDL) was similarly diminished, although neither parameter differed between transplant and control macrophages in the absence of stimulation. J:87639
|Molecular Note||Insertion of a PGK-neomycin resistance cassette into exon 6 disrupted the gene. Exon 6 encodes the p105 precursor of the p50 subunit of the encoded transcription factor. The authors predict that this allele produces a truncated polypeptide that cannot bind with DNA, or dimerize with itself or other kappaB binding motifs.|
|Mutations Made By|| |
Dr. David Baltimore, California Institute of Technology
When maintaining a live colony, these mice are bred as homozygotes.
When using the p50- mouse strain in a publication, please cite the originating article(s) and include JAX stock #006097 in your Materials and Methods section.