Overview

These Mre11^ATLD1/ATLD1 mice contain a mutation in the Mre11 gene, similar to that found in humans with ataxia-telangiectasia like disorder.

Donating Investigator

John Petrini, Memorial Sloan-Kettering Cancer Center

Genetic overview

Genetic Background	Generation

Mre11a^tm1Jpt

Allele Type	Gene Symbol	Gene Name
Targeted (Humanized sequence)	Mre11a	MRE11A homolog A, double strand break repair nuclease

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Research Applications

Cell Biology Research
Cancer Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

These Mre11^ATLD1/ATLD1 mice contain an A to T point mutation at nucleotide 1894, corresponding to human codon 633, of the meiotic recombination 11 homolog A (Mre11) gene. MRE11 is a component of a trimeric protein complex also containing Nbs1 and Rad50 which is involved in DNA double-strand break repair, cell cycle checkpoint activation, telomere maintenance, and meiotic recombination. This mutation introduces a premature stop codon, resulting in the truncation of 75 amino acids which produces a hypomorphic protein. This mutation is commonly found in human ataxia-telangiectasia like disorder (A-TLD) and Nijmegen Breakage Syndrome (NBS). A-TLD is characterized by defects in movement, coordination, and immune responses due to chromosomal instability. NBS is characterized by short stature, microcephaly, distinctive facial features, recurrent respiratory tract infections, an increased risk of cancer, and intellectual disability. Homozygous Mre11^ATLD1/ATLD1 females have severely reduced fertility, with decreased embryonic viability due to genome instability and cell cycle checkpoint defects. Homozygous males are viable and fertile. These mice, and cells derived from these mice, exhibit DNA double strand break repair defects, cell-cycle checkpoint defects, and chromosomal instability. These mice are not prone to malignancy including lymphomagenesis.

Development

A targeting construct was designed to introduce an A to T point mutation at nucleotide 1894, corresponding to human codon 633, resulting in a premature STOP codon in the meiotic recombination 11 homolog A (Mre11) gene, commonly found in human ataxia-telangiectasia like disorder (A-TLD). A neomycin resistance cassette was placed downstream of the mutation. This targeting construct was electroporated into 129S7/SvEvBrd-Hprt^b-m2-derived AB2.2 embryonic stem (ES) cells and correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric males were bred to C57BL/6 females. These Mre11^ATLD1/ATLD1 mice were maintained on a mixed background. Upon arrival at The Jackson Laboratory, mutant mice were bred to C57BL/6J mice (Stock No. 000664) for at least one generation to establish the colony.

Control Suggestions

Approximate Controls

101045 B6129SF2/J

Additional Information

Considerations for Choosing Controls

Selected References

Theunissen JW; Kaplan MI; Hunt PA; Williams BR; Ferguson DO; Alt FW; Petrini JH. 2003. Checkpoint failure and chromosomal instability without lymphomagenesis in Mre11(ATLD1/ATLD1) mice. Mol Cell 12(6):1511-23PubMed: 14690604 MGI: J:87088

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Genetics

Mre11a^tm1Jpt

Allele Symbol: Mre11a^tm1Jpt

Allele Name	targeted mutation 1, John H J Petrini
Allele Type	Targeted (Humanized sequence)
Allele Synonym(s)	Mre11^ATLD1
Gene Symbol and Name	Mre11a, MRE11A homolog A, double strand break repair nuclease
Gene Synonym(s)
Strain of Origin	129S7/SvEvBrd-Hprt^b-m2
Chromosome	9
Molecular Note	An A-to-T transversion point mutation was engineered at nucleotide 1894 of the coding sequence to recapitulate a nonsense mutation identified in human patients (codon 633). This mutation results in the truncation of 75 amino acids.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Cell Biology Research
- DNA Damage Response
- Cell Cycle Regulation
Cancer Research
- Other
  - DNA Repair

Mammalian Phenotype Terms by Genotype

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

Genotype: Mre11a^tm1Jpt/Mre11a^tm1Jpt
involves: 129S7/SvEvBrd

cellular phenotype

decreased cellular sensitivity to ionizing radiation
- at E13.5, E15.5, and P5, mice exhibit resistance to ionizing radiation-induced apoptosis in the retina and dentate gyrus compared to wild-type mice
- Normal - however, ionizing radiation-induced apoptosis in the proliferating embryonic ventricular zone is normal
- ionizing radiation-induced apoptosis in the thymus is reduced compared to in wild-type mice

The following phenotype relates to a compound genotype created using this strain

Genotype: Mre11a^tm1Jpt/Mre11a^tm1Jpt
involves: 129S7/SvEvBrd * C57BL/6

cellular phenotype

abnormal cell cycle checkpoint function
- checkpoint defects; MEFs fail to arrest or suffer attrition either in S phase or at the G2/M border
- MEFs exhibit defects in G1/S, intra-S-phase, and G2/M checkpoints after ionizing radiation induced DNA damage

chromosomal instability
- 18% of metaphases in splenocyte cultures exhibit aberrations
- 33% of early passage MEFs (p3) and 65% of late passage (greater than 5) MEFs show aberrant metaphases
- passage 7 MEFs show chromosomal instability; 43% vs. 19% of wild-type metaphases contain at least 1 aberration and the number of aberrations per metaphase is increased
- translocasions and fusions are seen in 5 of 32 early and 7 of 27 late passage MEFs

chromosome breakage

increased cellular sensitivity to ionizing radiation
- MEFs exhibit increased sensitivity to ionizing radiation
- mouse embryonic fibroblasts (MEFs) are sensitive to ionizing radiation

induced chromosome breakage
- MEFs are hypersensitive to irradiation-induced chromosome breakage

maternal effect
- embryonic viability is drastically reduced in homozygous mothers but not in heterozygous intercrosses, indicating a maternal effect on viability

mammalian phenotype

neoplasm
- Normal - inspite of cell cycle checkpoint failure and chromosomal instability, mice are not prone to malignancy including lymphomagenesis

reproductive system phenotype

reduced female fertility

References

Theunissen JW; Kaplan MI; Hunt PA; Williams BR; Ferguson DO; Alt FW; Petrini JH. 2003. Checkpoint failure and chromosomal instability without lymphomagenesis in Mre11(ATLD1/ATLD1) mice. Mol Cell 12(6):1511-23PubMed: 14690604 MGI: J:87088

Additional - Mre11a^tm1Jpt related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Mre11a-Alternate2
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, heterozygous females may be bred to homozygous males. Homozygous females are extremely subfertile.
- Additional Breeding and Husbandry Support
Mating System
- Heterozygote x Heterozygote
Citation
When using the B6;129S7-Mre11a^tm1Jpt/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #024172 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

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous for Mre11a<tm1Jpt>

Related Products and Services

Frozen Mouse Embryo	B6;129S7-Mre11a<tm1Jpt>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6;129S7-Mre11a<tm1Jpt>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6;129S7-Mre11a<tm1Jpt>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6;129S7-Mre11a<tm1Jpt>/J Frozen Embryo	$3373.50

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The Jackson Laboratory's Genotype Promise

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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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General Terms and Conditions

Questions about Terms of Use

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Mre11atm1Jpt

Allele Symbol: Mre11atm1Jpt

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Mre11atm1Jpt/Mre11atm1Jptinvolves: 129S7/SvEvBrd

cellular phenotype

Genotype: Mre11atm1Jpt/Mre11atm1Jptinvolves: 129S7/SvEvBrd * C57BL/6

cellular phenotype

mammalian phenotype

reproductive system phenotype

References

Additional - Mre11atm1Jpt related

Genotyping Protocols

Breeding Considerations

Mating System

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

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Mre11a^tm1Jpt

Allele Symbol: Mre11a^tm1Jpt

Genotype: Mre11a^tm1Jpt/Mre11a^tm1Jpt
involves: 129S7/SvEvBrd

Genotype: Mre11a^tm1Jpt/Mre11a^tm1Jpt
involves: 129S7/SvEvBrd * C57BL/6

Additional - Mre11a^tm1Jpt related