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- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
Description
Strain Information
Type Mutant Stock; Targeted Mutation; Mating System Homozygote x Homozygote (Female x Male) Species laboratory mouse Generation ?+N1F2 (20-MAY-08) Donating Investigator Yang Xu, University of California, San Diego Description
Mice homozygous for this targeted mutation are viable and fertile. They carry two phosphorylation site disruptions: Ser18 to Ala (S18A), and Ser23 to Ala (S23A). Trp53-dependent apoptosis is essentially abolished in thymocytes. These mice develop spontaneous tumors at approximately 1.5 years of age and a range of malignancies that are distinct from those found in animals carrying either a single S23A mutation or a complete knockout of the gene. This mutant mouse strain may be useful in studies of phosphorylation events in cancer development and apoptosis.Development
Missense mutations resulting in serine (Ser) to alanine (Ala) amino acid substitutions at codons 18 and 23 in exon 2 were engineered using site-directed mutagenesis. A targeting vector containing the Ser18/23Ala mutations and a loxP-flanked (floxed) PGK-Neo resistance cassette inserted into intron 4 was injected into 129S6/SvEvTac-derived TC-1 embryonic stem (ES) cells. F1 mutant heterozygous mice were bred to CMV-Cre transgenic mice on a C57BL/6 X 129 mixed genetic background to excise the floxed PGK-Neo cassette. Homozyotes were created by intercrossing heterozygotes.
Control Information
| Control | ||
|---|---|---|
| 101043 B6129SF1/J | (approximate) | |
| 101045 B6129SF2/J | (approximate) | |
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying Trp53tm2Xu allele
007218 B6.129S6-Trp53tm2Xu/J View Strains carrying Trp53tm2Xu (1 strain)
004301 129-Trp53tm1Holl/J 002080 129-Trp53tm1Tyj/J 002101 B6.129S2-Trp53tm1Tyj/J 007962 B6.FVB-Tg(MMTV-neu/OT-I/OT-II)CBnel Tg(Trp53R172H)8512Jmr/J 008191 B6;129S2-Trp53tm1Tyj Nf1tm1Tyj/J 002103 B6;129S2-Trp53tm1Tyj/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
Phenotype
Phenotype Information
Mammalian Phenotype Terms assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Trp53tm2Xu/Trp53tm2Xu
involves: 129S6/SvEvTac
- tumorigenesis
- altered tumor susceptibility/resistance (MGI Ref ID J:109354)
- mice are cancer prone but develop tumors in a wide spectrum of tissues, with a delayed onset compared with Trp53-null mice which develop thymic lymphomas primarily within 6 months of age
- abnormal tumor incidence (MGI Ref ID J:109354)
- mice develop leukemias, fibrosarcomas, granuloma and adenomas; these are rarely seen in Trp53tm1Tj homozygous mice
- hematopoietic system phenotype
- decreased T cell apoptosis (MGI Ref ID J:109354)
- thymocytes are essentially resistant to Trp53-mediated apoptosis
- decreased T cell proliferation (MGI Ref ID J:109354)
- proliferation of thymocytes after stimulation with PMA or Ionomycin is slower than Trp53tm1Tyj cells at the later time point, but similar to wild-type at the earlier time point
- immune system phenotype
- decreased T cell apoptosis (MGI Ref ID J:109354)
- thymocytes are essentially resistant to Trp53-mediated apoptosis
- decreased T cell proliferation (MGI Ref ID J:109354)
- proliferation of thymocytes after stimulation with PMA or Ionomycin is slower than Trp53tm1Tyj cells at the later time point, but similar to wild-type at the earlier time point
Research Applications
This mouse can be used to support research in many areas including:
Trp53 relatedApoptosis Research
Endogenous Regulators
Cancer Research
Increased Tumor Incidence (Adenomas)
Increased Tumor Incidence (Gonadal Tumors: ovarian)
Increased Tumor Incidence (Leukemia)
Increased Tumor Incidence (Lymphomas)
Increased Tumor Incidence (Other Tissues/Organs)
Tumor Suppressor Genes
Immunology and Inflammation Research
Intracellular Signaling Molecules
Apoptosis Research
Endogenous Regulators
Cancer Research
Increased Tumor Incidence (Lymphomas)
Increased Tumor Incidence (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)
Toxicology Research (drug/compound testing)
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Trp53tm2Xu | ||
|---|---|---|---|
| Allele Name | targeted mutation 2, Yang Xu | ||
| Common Name(s) | p53S18/23A; | ||
| Mutation Made By | Yang Xu, University of California, San Diego | ||
| Strain of Origin | 129S6/SvEvTac | ||
| ES Cell Line Name | TC-1 | ||
| ES Cell Line Strain | 129S6/SvEvTac | ||
| Gene Symbol and Name | Trp53, transformation related protein 53 | ||
| Chromosome | 11 | ||
| Gene Common Name(s) | FLJ92943; LFS1; p53; | ||
| Molecular Note | Site directed mutagenesis within exon 2 generated missense mutations at codons 18 and 23, resulting in the substitutions of both serines with alanines. A single loxP site remained in intron 4 after a floxed PGK-neo cassette was excised via cre-mediated recombination. Sequencing verified that only the S18/23A mutations were present in mutant mice. [MGI Ref ID J:109354] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Trp53tm2Xu, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
References
References
Selected Reference(s)
Chao C; Herr D; Chun J; Xu Y. 2006. Ser18 and 23 phosphorylation is required for p53-dependent apoptosis and tumor suppression. EMBO J 25(11):2615-22. [PubMed: 16757976] [MGI Ref ID J:109354]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $155.70 Female or Male Homozygous for Trp53tm2Xu *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $311.40 Homozygous for Trp53tm2Xu x Homozygous for Trp53tm2Xu
Supply Details
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
|---|---|
| Supply Notes |
|
Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $202.50 Female or Male Homozygous for Trp53tm2Xu *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $404.90 Homozygous for Trp53tm2Xu x Homozygous for Trp53tm2Xu
Supply Details
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
|---|---|
| Supply Notes |
|
Control Information
| Control | ||
|---|---|---|
| 101043 B6129SF1/J | (approximate) | |
| 101045 B6129SF2/J | (approximate) | |
| 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
View JAX® Mice & Services Conditions of Use.
Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.
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.
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 and Purchasing Information
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Contact Information
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