D2.129P2(B6)-Nfkb1^tm1Bal/SjJ

Stock number: 024702
Product name: p50^-
Research areas: Immunology, Inflammation and Autoimmunity Research

Description

Mice homozygous for Nfkb1^tm1Bal exhibit defective B cell responses, defective responses to infection, and also defects in basal and specific antibody production.

Detailed description

Mice homozygous for the Nfkb1^tm1Bal 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.

This strain is on a genetic background different from that on which the allele was first characterized. 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.

Development

Exon 6 of the Nfkb1 gene was disrupted by insertion of a vector containing the neo resistance gene. The 129-derived E14 ES cell line was used. This strain was crossed minimally to C57BL/6. The donating investigator then backcrossed to DBA/2J for 6 generations.

Allele

Symbol: Nfkb1^tm1Bal
Name: targeted mutation 1, David Baltimore
MGI accession ID: MGI:1857225
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Nfkb1
Marker name: nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105
Chromosome: 3
Strain of origin: 129P2/OlaHsd
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.
General note:

Effect of reconstitution with Nfkb1^tm1Bal 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 (Ldlr^tm1Her) were lethally irradiated and transplanted with bone marrow from Nfkb1^tm1Bal 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