Strain Name:

129-Trp53tm4Att/J

Stock Number:

021984

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Availability:

Cryopreserved - Ready for recovery

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In these p53LSL-25,26,53,54 mice both transactivation domains can be inactivated; 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;
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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-25,26,53,54 mice carry point mutations that result in the amino acid substitutions L25Q and W26S in exon 2, which encodes the first transcriptional activation domain of the protein, F53Q;F54S point mutation in exon 4, in the second transcriptional activation domain 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 express p53 protein with both transactivation domains inactivated, which cannot activate p53 target genes. Mice carrying the recombined allele exhibit defective cell cycle arrest or apoptosis activity in response to acute DNA damage and fail to suppress tumor development. When bred to Cre recombinase expressing mice, these mice could be used to generate tumor cells for engraftment experiments. 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, the L25Q and W26S mutations into exon 2, and the F53Q;F54S point mutations into exon 4. 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

Trp53tm4Att/Trp53tm4Att

        involves: 129S4/SvJae   (conditional)
  • cellular phenotype
  • decreased cellular sensitivity to gamma-irradiation
    • cell cycle is not arrested by gamma irradiation after treatment with adenovirus-cre   (MGI Ref ID J:173395)

The following phenotype relates to a compound genotype created using this strain.
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Trp53tm4Att/Trp53tm4Att Gt(ROSA)26Sortm1(cre/ERT2)Tyj/?

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

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Trp53tm4Att
Allele Name targeted mutation 4, Laura D Attardi
Allele Type Targeted (Floxed/Frt)
Common Name(s) p53LSL-25,26,53,54;
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 floxed puromycin/transcription stop cassette was inserted upstream of exon 2. In addition,mutations were inserted in exon 2 altering the codons for amino acid 25 from leucine to glutamine and amino acid 26 from tryptophan to serine. Further changes in exon 4 altered codon 53 from phenylalanine to glutamine and codon 54 from phenylalanine to serine. Both transactivation domains are incapacitated once the stop sequences are removed by cre expression. [MGI Ref ID J:173395]

Genotyping

Genotyping Information

Genotyping Protocols

Puromycin, Separated PCR
Trp53tm1Att-Alternate 3, Separated PCR
Trp53tm3Att, End Point Analysis


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

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]

Additional References

Trp53tm4Att related

Jiang D; Brady CA; Johnson TM; Lee EY; Park EJ; Scott MP; Attardi LD. 2011. Full p53 transcriptional activation potential is dispensable for tumor suppression in diverse lineages. Proc Natl Acad Sci U S A 108(41):17123-8. [PubMed: 21969549]  [MGI Ref ID J:177455]

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* $2085.00
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 11 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* $2710.50
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 11 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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