Strain Name:

129-Trp53tm1Holl/J

Stock Number:

004301

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Availability:

Cryopreserved - Ready for recovery

Use Restrictions Apply, see Terms of Use

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 Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Specieslaboratory mouse
 
Donating Investigator Monica Hollstein,   German Cancer Research Center (DKFZ)

Description
In this mutant mouse strain, the endogenous murine sequence for exons 4-9 of the targeted gene, which encode the DNA binding domain of the tumor suppressor protein, have been replaced with the homologous normal human sequence. Transcription is under the control of the endogenous mouse promoter. Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Homozygous mutant mice exhibit normal expression and functional activity of the chimeric gene. Homozygous mutant mice have normal immunodetectable levels of p53 protein accumulation in nuclei in response to UV-induced DNA damage. Thymocytes from mutant mice are as susceptible to gamma-irradiation-induced and dexamethaxone-induced apoptosis as wildtype thymocytes. This mutant mouse strain may be useful in studies related to in vivo spontaneous and induced mutation of the human TRP53 gene sequence, and pharmacological agents for altering DNA-binding activity in the human TRP53 gene.

Development
A targeting vector containing sequence from exons 4-9 of the normal human gene, neomycin resistance gene and floxed (loxP site flanked) herpes simplex virus thymidine kinase gene was utilized in the construction of this mutant. The construct was electroporated into 129P2/OlaHsd derived E14.1 embryonic stem (ES) cells. Cre recombinase was transiently expressed in ES cells to remove the loxP flanked neomycin/thymidine kinase sequence. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were backcrossed to 129 mice.

Control Information

  Control
   002448 129S1/SvImJ (approximate)
   000691 129X1/SvJ (approximate)
 
  Considerations for Choosing Controls

Related Strains

View Strains carrying other alleles of Trp53     (27 strains)

Strains carrying other alleles of TRP53
008045   B6;129-Trp53tm2Holl/J
View Strains carrying other alleles of TRP53     (1 strain)

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

Trp53tm1Holl/Trp53tm1Holl

        involves: 129P2/OlaHsd
  • cellular phenotype
  • *normal* cellular phenotype
    • irradiated mouse embryonic fibroblasts do not develop chromosomal translocations   (MGI Ref ID J:126497)

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

Trp53tm1Holl/Trp53tm1Holl

        involves: 129/Sv * 129P2/OlaHsd * C57BL/6
  • cellular phenotype
  • *normal* cellular phenotype
    • unlike in p53 null mice, p53 localization to UV irradiation and gamma-radiation induced apoptosis are normal   (MGI Ref ID J:68918)
  • tumorigenesis
  • *normal* tumorigenesis
    • unlike in p53 null mice, no tumors develop by 8 months of age   (MGI Ref ID J:68918)
View Research Applications

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

Apoptosis Research

Cancer Research
Toxicology
Tumor Suppressor Genes

Immunology, Inflammation and Autoimmunity Research
Intracellular Signaling Molecules

Research Tools
Apoptosis Research
Toxicology Research

Trp53tm1Holl related

Apoptosis Research
Endogenous Regulators

Cancer Research
Toxicology
Tumor Suppressor Genes

Immunology, Inflammation and Autoimmunity Research
Intracellular Signaling Molecules

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Trp53tm1Holl
Allele Name targeted mutation 1, Monica Hollstein
Allele Type Targeted
Common Name(s) HUPKI; p5372arg; p53KI; p53hki;
Mutation Made By Monica Hollstein,   German Cancer Research Center (DKFZ)
Strain of Origin129P2/OlaHsd
ES Cell Line NameE14.1
ES Cell Line Strain129P2/OlaHsd
Expressed Gene TRP53, tumor protein p53, Human
Gene Symbol and Name Trp53, transformation related protein 53
Chromosome 11
Gene Common Name(s) BCC7; LFS1; P53; p44;
Molecular Note Insertion of a loxP-flanked neomycin-thymidine kinase expression cassette replaced the mouse DNA-binding domain (exons 4-9) with the corresponding homologous segment of the normal human gene, leaving transcription under control of the endogenous promoter. Cre-mediated recombination in ES cells excised the neo-tk sequences. cDNA sequencing studies determined that transcripts from spleen of homozygous mutant mice carried the human sequence for exons 4-9, and that the gene is correctly spliced and transcribed. [MGI Ref ID J:68918]
 

Genotyping

Genotyping Information

Genotyping Protocols

Trp53tm1Holl, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Luo JL; Yang Q; Tong WM; Hergenhahn M; Wang ZQ; Hollstein M. 2001. Knock-in mice with a chimeric human/murine p53 gene develop normally and show wild-type p53 responses to DNA damaging agents: a new biomedical research tool. Oncogene 20(3):320-8. [PubMed: 11313961]  [MGI Ref ID J:68918]

Additional References

Luo JL; Tong WM; Yoon JH; Hergenhahn M; Koomagi R; Yang Q; Galendo D; Pfeifer GP; Wang ZQ; Hollstein M. 2001. UV-induced DNA Damage and Mutations in Hupki (Human p53 Knock-in) Mice Recapitulate p53 Hotspot Alterations in Sun-exposed Human Skin. Cancer Res 61(22):8158-63. [PubMed: 11719445]  [MGI Ref ID J:73194]

Trp53tm1Holl related

Feng L; Hollstein M; Xu Y. 2006. Ser46 phosphorylation regulates p53-dependent apoptosis and replicative senescence. Cell Cycle 5(23):2812-9. [PubMed: 17172844]  [MGI Ref ID J:191183]

Feng Z; Zhang C; Kang HJ; Sun Y; Wang H; Naqvi A; Frank AK; Rosenwaks Z; Murphy ME; Levine AJ; Hu W. 2011. Regulation of female reproduction by p53 and its family members. FASEB J 25(7):2245-55. [PubMed: 21402718]  [MGI Ref ID J:174329]

Frank AK; Leu JI; Zhou Y; Devarajan K; Nedelko T; Klein-Szanto A; Hollstein M; Murphy ME. 2011. The codon 72 polymorphism of p53 regulates interaction with NF-{kappa}B and transactivation of genes involved in immunity and inflammation. Mol Cell Biol 31(6):1201-13. [PubMed: 21245379]  [MGI Ref ID J:170615]

Jaworski M; Hailfinger S; Buchmann A; Hergenhahn M; Hollstein M; Ittrich C; Schwarz M. 2005. Human p53 knock-in (hupki) mice do not differ in liver tumor response from their counterparts with murine p53. Carcinogenesis 26(10):1829-34. [PubMed: 15917304]  [MGI Ref ID J:101711]

Liu DP; Song H; Xu Y. 2010. A common gain of function of p53 cancer mutants in inducing genetic instability. Oncogene 29(7):949-56. [PubMed: 19881536]  [MGI Ref ID J:160414]

Luo JL; Tong WM; Yoon JH; Hergenhahn M; Koomagi R; Yang Q; Galendo D; Pfeifer GP; Wang ZQ; Hollstein M. 2001. UV-induced DNA Damage and Mutations in Hupki (Human p53 Knock-in) Mice Recapitulate p53 Hotspot Alterations in Sun-exposed Human Skin. Cancer Res 61(22):8158-63. [PubMed: 11719445]  [MGI Ref ID J:73194]

Reinbold M; Luo JL; Nedelko T; Jerchow B; Murphy ME; Whibley C; Wei Q; Hollstein M. 2008. Common tumour p53 mutations in immortalized cells from Hupki mice heterozygous at codon 72. Oncogene 27(19):2788-94. [PubMed: 17998932]  [MGI Ref ID J:135505]

Song H; Hollstein M; Xu Y. 2007. p53 gain-of-function cancer mutants induce genetic instability by inactivating ATM. Nat Cell Biol 9(5):573-80. [PubMed: 17417627]  [MGI Ref ID J:126497]

Tong WM; Lee MK; Galendo D; Wang ZQ; Sabapathy K. 2006. Aflatoxin-B exposure does not lead to p53 mutations but results in enhanced liver cancer of Hupki (human p53 knock-in) mice. Int J Cancer 119(4):745-9. [PubMed: 16557586]  [MGI Ref ID J:112217]

Whibley C; Odell AF; Nedelko T; Balaburski G; Murphy M; Liu Z; Stevens L; Walker JH; Routledge M; Hollstein M. 2010. Wild-type and Hupki (human p53 knock-in) murine embryonic fibroblasts: p53/ARF pathway disruption in spontaneous escape from senescence. J Biol Chem 285(15):11326-35. [PubMed: 20118236]  [MGI Ref ID J:161187]

Zielinski B; Liu Z; Hollstein M; Hergenhahn M; Luo J. 2002. Mouse models for generating P53 gene mutation spectra. Toxicol Lett 134(1-3):31-7. [PubMed: 12191858]  [MGI Ref ID J:78492]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

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

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
   002448 129S1/SvImJ (approximate)
   000691 129X1/SvJ (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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