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

Former Names B6.129S-Trp53tm2Xu/J    (Changed: 15-JUL-08 ) Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation ?+N5F2p   Donating Investigator IMR Colony,   The Jackson Laboratory

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 also develop 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, cancer development and apoptosis.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development
A targeting vector containing Ser18 to Ala, and Ser23 to Ala mutations, in addition to a "floxed" PGK-Neo resistance cassette in exon 4, was injected into 129S6/SvEvTac-derived TC-1 embryonic stem (ES) cells. F1 mutant heterozygous mice were bred to CMV-Cre transgenic mice to excise the "floxed" PGK-Neo cassette. Homozyotes were created by intercrossing heterozygous mice prior to arrival at The Jackson Laboratory (as Stock No. 006980). Upon arrival, some mice were backcrossed to C57BL/6J for at least five generations to generate this congenic strain (Stock No. 007218).

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Trp53^tm2Xu allele

006980

B6;129-Trp53tm2Xu/J

View Strains carrying   Trp53^tm2Xu     (1 strain)

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
007962	B6.FVB-Tg(MMTV-neu/OT-I/OT-II)CBnel Tg(Trp53R172H)8512Jmr/J
008045	B6;129-Trp53tm2Holl/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
003262	STOCK Tg(Trp53A135V)L3Ber/J

View Strains carrying other alleles of Trp53     (20 strains)

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^tm2Xu/Trp53^tm2Xu

        involves: 129S6/SvEvTac

• tumorigenesis
• delayed tumor appearance (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
• increased tumor incidence (MGI Ref ID J:109354)
  • mice develop leukemias, fibrosarcomas, granuloma and adenomas; these are rarely seen in Trp53^tm1Tj homozygous mice
• hematopoietic system phenotype
• decreased T cell proliferation (MGI Ref ID J:109354)
  • proliferation of thymocytes after stimulation with PMA or Ionomycin is slower than Trp53^tm1Tyj 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 Trp53^tm1Tyj cells at the later time point, but similar to wild-type at the earlier time point

View Research Applications

Research Applications

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

Apoptosis Research
Endogenous Regulators

Cancer Research
Increased Tumor Incidence
      Adenomas
      Gonadal Tumors: ovarian
      Leukemia
      Lymphomas
      Other Tissues/Organs
Tumor Suppressor Genes

Immunology and Inflammation Research
Intracellular Signaling Molecules

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		Trp53tm2Xu
Allele Name		targeted mutation 2, Yang Xu
Allele Type		Targeted (knock-in)
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; MGC112612; 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

Trp53^tm2Xu, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

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

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.

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	Mutant mice were bred to C57BL/6J mice to generate this congenic strain. When maintaining the live congenic colony, homozygous mice may be bred.

Purchasing information

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

Pricing

Supply Details

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. 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. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 13 and 16 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). This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	000664 C57BL/6J
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.

---

Ordering and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

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.

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, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, 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 JACKSON, its agents or employees. In purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS 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 JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON 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 JACKSON, 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 JACKSON, 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 or services by JACKSON.