B6;129P-Nfkb1^tm1Bal/J

Stock number: 002849
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.

Development

Exon 6 of the Nfkb1 gene was disrupted by insertion of a vector containing the neo resistance gene. The construct was electroporated into 129P2/OlaHsd-derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were bred to crossed to C57BL/6J.

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