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 tumorgenesis. 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)||Xrcc5tm1Nus; targeted mutation 1, Andre Nussenzweig|
|Gene Symbol and Name||Xrcc5, X-ray repair complementing defective repair in Chinese hamster cells 5|
|Gene Synonym(s)||NFIV; AI314015; KARP-1; KARP1; KU80; Ku86; KUB2; expressed sequence AI314015; Kup80; Ku80|
|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.
|Heterozygous or wildtype for Xrcc5<tm1Nus>|
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
|Frozen Mouse Embryo||$2,595.00 per straw or vial|
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