Nfkb1^tm1Bal
Targeted Allele Detail

Summary

• Symbol: Nfkb1^tm1Bal
• Name: nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105; targeted mutation 1, David Baltimore
• MGI ID: MGI:1857225
• Synonyms: Nfkappab1-, NF-kappaB1^-, NFkappaB1⁰, NF-kappaB1 KO, NF-kappaB^tm1Bal, Nfkb1-, p105^-, p50^-, p50^KO
• Gene: Nfkb1 Location: Chr3:135290416-135397308 bp, - strand Genetic Position: Chr3, 62.82 cM
• Alliance: Nfkb1^tm1Bal page

Mutation origin

• Germline Transmission: Earliest citation of germline transmission: J:37184
• Parent Cell Line: E14 (ES Cell)
• Strain of Origin: 129P2/OlaHsd

Mutation description

• Allele Type: Targeted (Null/knockout)
• Mutation: Insertion
• Mutation details: 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. (J:37184)

Expression

In Mice Carrying this Mutation:	2 RNA-Seq or microarray experiment(s)
In Structures Affected by this Mutation:	8 anatomical structure(s)

Find Mice (IMSR)

• Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)
• Carrying this Mutation: Mouse Strains: 3 strains available Cell Lines: 0 lines available
• Carrying any Nfkb1 Mutation: 102 strains or lines available

Notes

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

References

• Original: J:37184 Sha WC, et al., Targeted disruption of the p50 subunit of NF-kappa B leads to multifocal defects in immune responses. Cell. 1995 Jan 27;80(2):321-30
• All: 260 reference(s)