| Primary Identifier | MGI:1857225 | Allele Type | Targeted |
| Attribute String | Null/knockout | Gene | Nfkb1 |
| Transmission | Germline | Strain of Origin | 129P2/OlaHsd |
| Is Recombinase | false | Is Wild Type | false |
| description | Effect of reconstitution with Nfkb1tm1Bal homozygous hematopoietic cells on atherogenesis in atherosclerosis prone miceTo 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 |
| molecularNote | 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. |
