Description

Strain Information

Type Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse   Donating Investigator Monica Hollstein,   German Cancer Research Center

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
	000691 129X1/SvJ
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Trp53

002080	129-Trp53tm1Tyj/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
007962	B6.FVB-Tg(MMTV-neu/OT-I/OT-II)CBnel Tg(Trp53R172H)8512Jmr/J
006980	B6;129-Trp53tm2Xu/J
008191	B6;129S2-Trp53tm1Tyj Nf1tm1Tyj/J
002103	B6;129S2-Trp53tm1Tyj/J
008181	B6;129S4-Trp53tm4Tyj/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
003262	STOCK Tg(Trp53A135V)L3Ber/J

View Strains carrying other alleles of Trp53     (17 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Trp53^tm1Holl/Trp53^tm1Holl

        involves: 129P2/OlaHsd

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

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Trp53^tm1Holl/Trp53^tm1Holl

        involves: 129/Sv * 129P2/OlaHsd * C57BL/6

• cellular phenotype
• *normal* cellular phenotype (MGI Ref ID J:68918)
  • unlike in p53 null mice, p53 localization to UV irradiation and gamma-radiation induced apoptosis are normal
• tumorigenesis
• *normal* tumorigenesis (MGI Ref ID J:68918)
  • unlike in p53 null mice, no tumors develop by 8 months of age

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 and Inflammation Research
Intracellular Signaling Molecules

Research Tools
Apoptosis Research
Toxicology Research

Trp53 related

Cancer Research
Increased Tumor Incidence (Lymphomas)
Increased Tumor Incidence (Other Tissues/Organs: osteosarcoma)

Mouse/Human Gene Homologs
Li-Fraumeni syndrome

Research Tools
Toxicology Research (B and T cell deficiency) (xenograft transplant host)
Toxicology Research (drug/compound testing)

Trp53^tm1Holl related

Apoptosis Research
Endogenous Regulators

Cancer Research
Toxicology
Tumor Suppressor Genes

Immunology and Inflammation Research
Intracellular Signaling Molecules

Genes & Alleles

Gene & Allele Information

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
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14.1
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Trp53, transformation related protein 53
Chromosome		11
Gene Common Name(s)		FLJ92943; LFS1; p53;
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

Trp53^tm1Holl, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

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]

Trp53^tm1Holl related

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]

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]

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

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	000691 129X1/SvJ
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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.

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Ordering and Purchasing Information

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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.
P53 Mice are subject to U.S. 5,569,824 and corresponding license requirements.

For additional Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (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 with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

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In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.