Overview

Also Known As: Ku80-

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.

Donating Investigator

Andre Nussenzweig, CCR, NCI, National Institutes of Health

Genetic overview

Genetic Background	Generation

Xrcc5^tm1Nus

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Xrcc5	X-ray repair complementing defective repair in Chinese hamster cells 5

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Research Applications

Developmental Biology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

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.

Development

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.

Selected References

Nussenzweig A; Chen C; da Costa Soares V; Sanchez M; Sokol K; Nussenzweig MC; Li GC. 1996. Requirement for Ku80 in growth and immunoglobulin V(D)J recombination. Nature 382(6591):551-5PubMed: 8700231 MGI: J:72368

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Genetics

Xrcc5^tm1Nus

Allele Symbol: Xrcc5^tm1Nus

Allele Name	targeted mutation 1, Andre Nussenzweig
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Xrcc5^tm1Nus; 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⁺
Chromosome	1
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

Disease/Phenotype

Disease Terms

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Genotype: Xrcc5^tm1Nus related

Developmental Biology Research
- Growth Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Xrcc5^tm1Nus/Xrcc5^tm1Nus
involves: 129S1/Sv * 129X1/SvJ

behavior/neurological phenotype

abnormal maternal nurturing
- Xrcc-deficient females are unable to sustain their pups which die in a few days unless nursed by a foster mother

homeostasis/metabolism phenotype

abnormal double-strand DNA break repair
- cells from null mice show a reduced ability to rejoin DNA double-strand breaks than wild-type

immune system phenotype

abnormal class switch recombination
- class switching recombination (CSR)-induced Smu internal deletion is impaired

abnormal humoral immune response
- B cell proliferation and apoptosis following LSP or Il-4 treatment was severely impaired even in cells that had undergone several rounds of cell division

spleen hypoplasia
- spleen contains over 50-fold less cells than wild-type

thymus hypoplasia
- thymus has over 100-fold less cells than wild-type

mortality/aging

postnatal lethality, incomplete penetrance
- 50% of homozygotes fail to thrive and die within 3 days of birth; survival improves to 80% when the larger wild-type and heterozygous littermates are removed

reproductive system phenotype

decreased litter size

cellular phenotype

abnormal double-strand DNA break repair
- cells from null mice show a reduced ability to rejoin DNA double-strand breaks than wild-type

increased cellular sensitivity to ionizing radiation
- after exposure to ionizing radiation, bone marrow cells display less colony formation compared to wild-type

endocrine/exocrine gland phenotype

thymus hypoplasia
- thymus has over 100-fold less cells than wild-type

growth/size/body region phenotype

decreased body size
- homozygotes are smaller than wild-type or heterozygous littermates

fetal growth retardation
- growth retardation is noted first at E15.5 and size difference is significant at E17.5, increasing to ~40% at birth

proportional dwarf
- newborns are 40-60% smaller than wild-type and heterozygous littermates and during 6-month observation grew but maintained a body weight of 40-60% that of controls; Xrcc5-null mice are proportional dwarfs

hematopoietic system phenotype

abnormal bone marrow cell morphology/development
- bone marrow reduced lymphoid cellularity compared to wild-type

abnormal class switch recombination
- class switching recombination (CSR)-induced Smu internal deletion is impaired

spleen hypoplasia
- spleen contains over 50-fold less cells than wild-type

thymus hypoplasia
- thymus has over 100-fold less cells than wild-type

References

Nussenzweig A; Chen C; da Costa Soares V; Sanchez M; Sokol K; Nussenzweig MC; Li GC. 1996. Requirement for Ku80 in growth and immunoglobulin V(D)J recombination. Nature 382(6591):551-5PubMed: 8700231 MGI: J:72368

Additional References

Difilippantonio MJ; Zhu J; Chen HT; Meffre E; Nussenzweig MC; Max EE; Ried T; Nussenzweig A. 2000. DNA repair protein Ku80 suppresses chromosomal aberrations and malignant transformation. Nature 404(6777):510-4PubMed: 10761921 MGI: J:72312
Difilippantonio MJ; Petersen S; Chen HT; Johnson R; Jasin M; Kanaar R; Ried T; Nussenzweig A. 2002. Evidence for replicative repair of DNA double-strand breaks leading to oncogenic translocation and gene amplification. J Exp Med 196(4):469-80PubMed: 12186839 MGI: J:78496

Additional - Xrcc5^tm1Nus related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR: Xrcc5^tm1Nus
- Genotyping resources and troubleshooting
Breeding Considerations

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.
- Additional Breeding and Husbandry Support
Citation
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.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

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Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	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.

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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Also Known As: Ku80-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Selected References

Xrcc5tm1Nus

Allele Symbol: Xrcc5tm1Nus

Disease Terms

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Genotype: Xrcc5tm1Nus related

Mammalian Phenotype Terms by Genotype

Genotype: Xrcc5tm1Nus/Xrcc5tm1Nusinvolves: 129S1/Sv * 129X1/SvJ

behavior/neurological phenotype

homeostasis/metabolism phenotype

immune system phenotype

mortality/aging

reproductive system phenotype

cellular phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

hematopoietic system phenotype

References

Additional References

Additional - Xrcc5tm1Nus related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Xrcc5^tm1Nus

Allele Symbol: Xrcc5^tm1Nus

Genotype: Xrcc5^tm1Nus related

Genotype: Xrcc5^tm1Nus/Xrcc5^tm1Nus
involves: 129S1/Sv * 129X1/SvJ

Additional - Xrcc5^tm1Nus related