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- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- 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. Visit our online Nomenclature tutorial. Species laboratory mouse Generation ?+F1p (24-JUL-05)
Generation DefinitionsDonating 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
Strains carrying other alleles of Trp53
002080 129-Trp53tm1Tyj/J 008652 129S-Trp53tm2Tyj/J 008651 129S-Trp53tm3Tyj/J 008462 B6.129P2-Trp53tm1Brn/J 002101 B6.129S2-Trp53tm1Tyj/J 008183 B6.129S4(Cg)-Trp53tm2.1Tyj/J 008182 B6.129S4-Trp53tm3.1Tyj/J 007218 B6.129S6-Trp53tm2Xu/J 011109 B6.Cg-Trp53tm2Glo/Kvm 018285 B6.Cg-Tyrc-2J Trp53tm1Tyj Hrhr/J 007962 B6.FVB-Tg(MMTV-neu/OT-I/OT-II)CBnel Tg(Trp53R172H)8512Jmr/J 017767 B6;129-Trp53tm1.1Dgk/J 008045 B6;129-Trp53tm2Holl/J 006980 B6;129-Trp53tm2Xu/J 008191 B6;129S2-Trp53tm1Tyj Nf1tm1Tyj/J 002103 B6;129S2-Trp53tm1Tyj/J 008181 B6;129S4-Trp53tm4Tyj/J 008361 B6;129S4-Trp53tm5Tyj/J 002526 C.129S2(B6)-Trp53tm1Tyj/J 002547 C3Ou.129S2(B6)-Trp53tm1Tyj/J 002899 FVB.129S2(B6)-Trp53tm1Tyj/J 002659 FVB/N-Tg(Trp53R172H)8512Jmr/J 002660 FVB/N-Tg(Trp53R172L)4491Jmr/J 017530 STOCK Iis2tm2(ACTB-tdTomato,-EGFP)Luo Trp53tm1Tyj Nf1tm1Par/J 012620 STOCK Trp53tm1Brd Brca1tm1Aash Tg(LGB-cre)74Acl/J 003262 STOCK Tg(Trp53A135V)L3Ber/J View Strains carrying other alleles of Trp53 (26 strains)
008045 B6;129-Trp53tm2Holl/J
Phenotype
Phenotype Information
- 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 (TP53)
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 may relate to a genetic background differing from this JAX® Mice strain.
Trp53tm1Holl/Trp53tm1Holl
involves: 129/Sv * 129P2/OlaHsd * C57BL/6This mouse can be used to support research in many areas including:
Trp53tm1Holl relatedCancer Research
Toxicology
Tumor Suppressor Genes
Immunology, Inflammation and Autoimmunity Research
Intracellular Signaling Molecules
Research Tools
Apoptosis Research
Toxicology Research
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 (knock-in) | ||
| Common Name(s) | HUPKI; p5372arg; p53KI; p53hki; | ||
| Mutation Made By | Monica Hollstein, German Cancer Research Center (DKFZ) | ||
| Strain of Origin | 129P2/OlaHsd | ||
| ES Cell Line Name | E14.1 | ||
| ES Cell Line Strain | 129P2/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 relatedFeng 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.Colony Maintenance
Diet Information LabDiet® 5K52/5K67
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
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Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2450.00 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 |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $3185.00 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).
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Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
General Supply Notes
- Genomic DNA is available for this strain from the Mouse DNA Resource.
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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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.
See Terms of Use tab for General Terms and Conditions
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.Ordering Information
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For Licensing and Use Restrictions view the link(s) below:
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Contact information
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| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
JAX® Mice, Products & Services Conditions of Use
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.No Warranty
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