Strain Name:

129-Trp53tm1Att/J

Stock Number:

022070

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Availability:

Cryopreserved - Ready for recovery

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In these p53LSL-25,26 mice, which carry a mutation in the first transcriptional activation domain, expression of the mutant TRP53 protein is silenced until Cre recombinase mediates excision of the upstream floxed STOP cassette. These mice may be useful in studies of p53 function and the role of p53 as a transcriptional activator in tumor suppression.

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Coisogenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Specieslaboratory mouse
 
Donating Investigator Laura Attardi,   Stanford University Medical Center

Description
The Trp53, transformation related protein 53, gene encodes the p53 tumor suppressor protein, which functions as a transcription factor regulating expression of more than 100 target genes. Mutations resulting in inactivation of p53 protein facilitates tumor progression. These p53LSL-25,26 mice carry amino acid substitutions L25Q and W26S in exon 2, which encodes the first transcriptional activation domain of the protein, and a floxed STOP cassette upstream of exon 2. Expression of the mutant TRP53 protein is silenced until Cre recombinase mediates excision of the floxed STOP cassette. After Cre recombinase mediated removal of the floxed STOP cassette cells from the resulting mice exhibit impaired transactivation of many p53 target genes, including Cdkn1a, Pmaip1, and Bbc3, but retains the ability to activate a small subset of target genes, including Bax. Mice that are homozygous for the targeted mutation are viable, but have decreased fertility.

For example, when bred to B6.129-Gt(ROSA)26Sortm1(cre/ERT2)Tyj/J mice (Stock No. 008463) tamoxifen induced Cre recombinase expression in offspring reduces apoptosis following radiation treatment.

Development
A targeting vector designed by Dr. Laura D. Attardi (Stanford University School of Medicine) containing a floxed STOP element with 4 poly adenylation sites, and a puromycin resistance cassette, was utilized to insert the floxed STOP cassette upstream of exon 2 and the L25Q and W26S mutations into exon 2. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to 129 Sv/J mice. Upon arrival at The Jackson Laboratory, the mice were crossed to 129S1/SvImJ (Stock No. 002448) at least once to establish the colony.

Control Information

  Control
   Wild-type from the colony
   002448 129S1/SvImJ (approximate)
 
  Considerations for Choosing Controls

Related Strains

View Strains carrying other alleles of Trp53     (27 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Adrenocortical Carcinoma, Hereditary; ADCC   (TP53)
Basal Cell Carcinoma, Susceptibility to, 7; BCC7   (TP53)
Breast Cancer   (TP53)
Colorectal Cancer; CRC   (TP53)
Glioma Susceptibility 1; GLM1   (TP53)
Hepatocellular Carcinoma   (TP53)
Li-Fraumeni Syndrome 1; LFS1   (TP53)
Nasopharyngeal Carcinoma   (TP53)
Osteogenic Sarcoma   (TP53)
Pancreatic Cancer   (TP53)
Papilloma of Choroid Plexus; CPP   (TP53)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Trp53tm1Att/Trp53tm1Att

        involves: 129S4/SvJae   (conditional)
  • cellular phenotype
  • abnormal cell cycle
    • there is only a small reduction in the number of cells in S phase following adenoviral cre infection, and this percentage is still higher than in wild-type MEFs   (MGI Ref ID J:96433)
    • abnormal cell cycle checkpoint function
      • MEFs infected with adenoviral cre and treated with doxorubicin show only a moderate decrease in the percentage of cells in S phase indicating an impaired G1 arrest response   (MGI Ref ID J:96433)
  • decreased cellular sensitivity to gamma-irradiation
    • cell cycle is not arrested by gamma irradiation after treatment with adenovirus-cre   (MGI Ref ID J:173395)
  • decreased cellular sensitivity to ultraviolet irradiation
    • following adenoviral cre infection, MEFs remain refractory to UV-C-induced cell death but not hypoxia-induced cell death   (MGI Ref ID J:96433)

Trp53tm1Att/Trp53tm1Att

        involves: 129S4/SvJae
  • cellular phenotype
  • abnormal cell cycle
    • similar to Trp53 null cells, the percentage of cells in S phase is increased compared to wild-type cells   (MGI Ref ID J:96433)
  • abnormal cell death
    • in the absence of cre, MEFs are refractory to stress-induced cell death   (MGI Ref ID J:96433)

The following phenotype relates to a compound genotype created using this strain.
Contact JAX® Services jaxservices@jax.org for customized breeding options.

Trp53tm1Att/Trp53tm1Att Gt(ROSA)26Sortm1(cre/ERT2)Tyj/?

        involves: 129S4/SvJae   (conditional)
  • cellular phenotype
  • decreased apoptosis
    • no apoptosis in mice treated with tamoxifen measured 6 hours after radiation treatment   (MGI Ref ID J:173395)

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Trp53tm1Att
Allele Name targeted mutation 1, Laura D Attardi
Allele Type Targeted (Conditional ready (e.g. floxed), No functional change)
Common Name(s) Trp53LSL-QS;
Strain of Origin129S4/SvJae
Gene Symbol and Name Trp53, transformation related protein 53
Chromosome 11
Gene Common Name(s) BCC7; LFS1; P53; p44;
Molecular Note A knock in strategy was used to introduce a loxP-Stop-loxP transcriptional stop element upstream of exon 2 and L25Q and W26S substitutions into exon 2. Northern and Western blots of mutant MEFs treated with adeno-virus cre demonstrated that transcript and protein were expressed, respectively. No expression is seen without Cre expression. [MGI Ref ID J:96433]

Genotyping

Genotyping Information

Genotyping Protocols

Trp53tm1,3,4Att, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Johnson TM; Hammond EM; Giaccia A; Attardi LD. 2005. The p53QS transactivation-deficient mutant shows stress-specific apoptotic activity and induces embryonic lethality. Nat Genet 37(2):145-52. [PubMed: 15654339]  [MGI Ref ID J:96433]

Additional References

Trp53tm1Att related

Brady CA; Jiang D; Mello SS; Johnson TM; Jarvis LA; Kozak MM; Kenzelmann Broz D; Basak S; Park EJ; McLaughlin ME; Karnezis AN; Attardi LD. 2011. Distinct p53 transcriptional programs dictate acute DNA-damage responses and tumor suppression. Cell 145(4):571-83. [PubMed: 21565614]  [MGI Ref ID J:173395]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, these mice can be bred as heterozygotes. Homozygotes exhibit decreased fertility.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2525.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3283.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Wild-type from the colony
   002448 129S1/SvImJ (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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