Description

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Heterozygote x Heterozygote         (Female x Male)   29-AUG-09 Species laboratory mouse Generation F?+1 (18-NOV-09)   Donating Investigator Tyler Jacks,   Massachusetts Institute of Technology

Description
These targeted mutant mice carry a loxP-flanked STOP cassette in intron 1 that blocks expression of the gene. Both heterozygotes and homozygotes are prone to the development of tumors (primarily spontaneous thymic lymphomas and sarcomas). The latency is significantly shorter in homozygotes than in wildtype mice. Homozygotes have reduced fertility. Upon Cre-mediated recombination, the STOP cassette can be excised, leading to restoration of gene expression. This strain permits temporal control of this tumor suppressor gene, and enables studies of tumorigenesis.

Development
A loxP-flanked STOP cassette was introduced to intron 1 to block expression of the gene. The targeting vector was introduced to 129S4/SvJae-derived J1 embryonic stem (ES) cells. This line was maintained on a mixed 129S4/SvJae and C57BL/6 background by the donating investigator.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Trp53

004301	129-Trp53tm1Holl/J
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
007962	B6.FVB-Tg(MMTV-neu/OT-I/OT-II)CBnel Tg(Trp53R172H)8512Jmr/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
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     (21 strains)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

Trp53^tm5Tyj/Trp53^tm5Tyj

        involves: 129S4/SvJae

• cellular phenotype
• abnormal cell cycle (MGI Ref ID J:96433)
  • similar to Trp53 null cells, the percentage of cells in S phase is increased compared to wild-type cells
• abnormal cell death (MGI Ref ID J:118233)
  • lack cell-culture-induced senescence
  • in the absence of cre, MEFs are refractory to stress-induced cell death
• abnormal chromosome number (MGI Ref ID J:118233)
  • marked genetic instability similar to that seen in Trp53^tm1Tyj homozygous cells

Trp53^tm5Tyj/Trp53^tm5Tyj

        involves: 129S4/SvJae   (conditional)

• cellular phenotype
• *normal* cellular phenotype (MGI Ref ID J:96433)
  • infection with adenoviral cre restores normal DNA damage-induce G1 arrest response and stress-induced apoptotic responses

View Research Applications

Research Applications

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

Cancer Research
Increased Tumor Incidence
      Lymphomas: thymic
      Other Tissues/Organs: osteosarcoma
Tumor Suppressor Genes

Research Tools
Cre-lox System
      loxP-flanked Sequences
Developmental Biology Research
      Cre-lox System

Trp53 related

Apoptosis Research
Endogenous Regulators

Cancer Research
Increased Tumor Incidence
      Lymphomas
      Other Tissues/Organs: osteosarcoma
Toxicology
Tumor Suppressor Genes

Immunology and Inflammation Research
Intracellular Signaling Molecules

Mouse/Human Gene Homologs
Li-Fraumeni syndrome

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

Genes & Alleles

Gene & Allele Information

Allele Symbol		Trp53tm5Tyj
Allele Name		targeted mutation 5, Tyler Jacks
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		p53-LSL; p53LSL;
Mutation Made By		Tyler Jacks,   Massachusetts Institute of Technology
Strain of Origin		129S4/SvJae
ES Cell Line Name		J1
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Trp53, transformation related protein 53
Chromosome		11
Gene Common Name(s)		FLJ92943; LFS1; MGC112612; p53;
Molecular Note		A lox-stop-lox cassette is integrated into intron 1 disrupting expression of the gene. [MGI Ref ID J:118233]

Genotyping

Genotyping Information

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

Ventura A; Kirsch DG; McLaughlin ME; Tuveson DA; Grimm J; Lintault L; Newman J; Reczek EE; Weissleder R; Jacks T. 2007. Restoration of p53 function leads to tumour regression in vivo. Nature 445(7128):661-5. [PubMed: 17251932]  [MGI Ref ID J:118233]

Additional References

Trp53^tm5Tyj related

Beekman C; Nichane M; De Clercq S; Maetens M; Floss T; Wurst W; Bellefroid E; Marine JC. 2006. Evolutionarily conserved role of nucleostemin: controlling proliferation of stem/progenitor cells during early vertebrate development. Mol Cell Biol 26(24):9291-301. [PubMed: 17000755]  [MGI Ref ID J:118144]

Francoz S; Froment P; Bogaerts S; De Clercq S; Maetens M; Doumont G; Bellefroid E; Marine JC. 2006. Mdm4 and Mdm2 cooperate to inhibit p53 activity in proliferating and quiescent cells in vivo. Proc Natl Acad Sci U S A 103(9):3232-7. [PubMed: 16492744]  [MGI Ref ID J:120591]

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]

Johnson TM; Meade K; Pathak N; Marques MR; Attardi LD. 2008. Knockin mice expressing a chimeric p53 protein reveal mechanistic differences in how p53 triggers apoptosis and senescence. Proc Natl Acad Sci U S A 105(4):1215-20. [PubMed: 18216268]  [MGI Ref ID J:131856]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	When maintained as a live colony, heterozygotes or homozygotes may be bred. Homozygous fertility is slightly reduced. Both heterozygotes and homozygotes are prone to tumor development.
Mating System	Heterozygote x Heterozygote         (Female x Male)   29-AUG-09
Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

 

This strain is currently Under Development for Production.
To register your interest in this strain go to the Strain Interest Form.

Estimated Available for Sale Date: 30-NOV-09

Please note: Estimated available for sale dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for sale depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain/interest registered.

View All Strains Under Development and On Hold

Pricing

Supply Details

Standard Supply	Under Development for Distribution Colony
Supply Notes	Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type from the colony
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.

Payment Terms and Conditions

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.

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Ordering and Purchasing Information

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Contact Information
Orders & Technical Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

OncoMouse^® requires a license from DuPont, see Licenses for Strains with OncoMouse^® Technology.
P53 Mice are subject to U.S. 5,569,824 and corresponding license requirements.

Contact information

General inquiries

Contracts Administration

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.

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