These Xrcc5 knock-out mice exhibit growth deficiency including decreased size of spleen, lymph nodes and thymus with curtailed T cell and B cell development.
Andre Nussenzweig, CCR, NCI, National Institutes of Health
Mice that are homozygous for the targeted mutation are viable, fertile, but are 40-60% the size of normal mice. No Xrcc5 protein product is detected. The growth deficiency phenotype is exhibited as early as E15.5. Organ weights, excepting lymphoid organs, are proportional to total body weight. Histological analysis shows decreased size of spleen, lymph nodes and thymus. T cell and B cell development is arrested at early precursor stages and a deficiency in V(D)J rearrangement is exhibited. B cell maturation stops at the B220+CD43+ stage. Only CD4-CD8- cells are found in the thymus. Primary embryonic fibroblasts (MEFs) have slower growth and early loss of proliferating cells. Early appearance of non-dividing cells in MEF cultures suggest early onset senescence. Karyotypes reveal increased chromosomal aberrations. Breaks or translocations occur in 83% of metaphases, polyploidy in 15%. Although cells from the mutant mice display chromosomal instability, these mice do not display early tumorigenesis. Litters must be fostered because homozygous mutant female mice are unable to sustain newborn pups. Survival of homozygous mutant mice is 80% when the larger heterozygous mutant and wildtype littermates are removed. This mutant mouse strain represents a model that may be useful in studies related to DNA repair and aging.
A targeting vector containing a neomycin resistance gene driven by the phosphoglycerate kinase promoter was used to disrupt 3.4 kb of the targeted gene, including 100 bp of the promoter and first 2 exons. The construct was electroporated into 129 derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were backcrossed to C57BL/6 mice.
|Allele Name||targeted mutation 1, Andre Nussenzweig|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Ku80-; Ku86-; Xrcc5tm1Gcl|
|Gene Symbol and Name||Xrcc5, X-ray repair complementing defective repair in Chinese hamster cells 5|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|Molecular Note||A neomycin resistance cassette replaced 3.4 kb of the gene, including 100 bp of the promoter region.|
|Mutations Made By|| |
Andre Nussenzweig, CCR, NCI, National Institutes of Health
This strain originated on a B6;129 background, has been backcrossed for 9 generations on the C57BL/6 background and is maintained as a heterozygote.
When using the Ku80- mouse strain in a publication, please cite the originating article(s) and include JAX stock #004361 in your Materials and Methods section.
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