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Strain Name:
B6.C-Trp53tm1.1Hwan/Mmjax
Stock Number:
076324-JAX
Citation ID:
RRID:MMRRC_076324-JAX
Other Names:
Trp53 R334H KI

Strain Information

QUALITY CONTROL OF B6.C-Trp53tm1.1Hwan/Mmjax  |  The Jackson Laboratory
Last Updated:
Strain Data and Information Information by Submitter Assessed by MMRRC1,2
Published Provided
Allele-specific genotype3n.d.
Genetic backgroundn.d.
Viability of genotypes available for distributionn.d.
Specific Pathogen- Status n.d.
Recoverability of cryopreserved sperm/embryos4 n.d.
Gene or allele sequence3n.d.
Gene or allele expression3n.d.
Gene or allele function3n.d.
Observable and/or measurable phenotypesn.d.
Fertility of genotypes available for distribution n.d.
Fecundity/breeding performance n.d.

1 When indicated as "assessed by MMRRC" ("YES"), please note that the information presented on this strain is to the best of our knowledge correct and up-to-date at the the MMRRC Distribution Center assigned to maintain and distribute this strain. This information is subject to change due to breeding, maintenance, and other actions. Please direct any questions on the information presented in this table to the MMRRC Distribution Center.

2 If an assessment has not been performed by the MMRRC (as indicated by "NO"), investigators may request specific testing for a fee. Requests should be submitted directly to the MMRRC Distribution Center assigned to the management, archiving, and distribution of the strain. A full listing of available testing and analytical services is available at https://www.mmrrc.org/about/services.php.

3 This information may or may not apply to each individual engineered allele (e.g., Cre, FlpO) present in the strain.

4 Recovery refers to thawing, in vitro fertilization (IVF), and/or embryo culture leading to live offspring.

Trp53tm1.1Hwan
Name: transformation related protein 53; targeted mutation 1.1, Paul M Hwang
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 11
Alteration at locus: Knock-In
Trp53
Name: transformation related protein 53
Synonyms: p53, p44
Type: Gene
Species: Mouse
Chromosome: 11
NCBI: 22059
Homologene: 460
Genetic Alterations
Targeted G-to-A missense mutation in exon 10 of Trp53 (c.1001G>A) followed by CMV-Cre-mediated deletion of the loxP-flanked neomycin resistance cassette. The mutation results in an arginine-to-histidine substitution at amino acid 334 (R334H), corresponding to the human TP53 R337H mutation to model Li-Fraumeni syndrome.
ES Cell Line
PRX-B6N
Phenotype

Trp53 R334H knock-in mice display no overt phenotype under baseline conditions. Heterozygous and homozygous mutant mice develop normally, similar to wild-type mice. The R334H mutation does not significantly alter lifespan, spontaneous cancer incidence, or cancer spectrum compared with wild-type mice, although a trend toward fewer female homozygous mice than expected was reported.

Conditional phenotype: Following diethylnitrosamine (DEN) exposure, mice exhibit increased susceptibility to liver carcinogenesis in a mutant allele dose-dependent manner. Mutant mice develop increased numbers and sizes of liver tumors, and homozygous mice have significantly increased liver weight relative to body weight and an increased incidence of liver carcinomas compared with wild-type mice.

Homozygous mice exposed to DEN exhibited increased DNA damage but decreased cell-cycle regulation in the liver.

The R334H mutation also results in reduced p53 oligomerization. Homozygous mutant liver tissue shows decreased p53 tetramer and dimer formation and increased monomer formation following DEN treatment, with significantly reduced tetramers also observed following doxorubicin treatment. Following whole-body γ-irradiation, mutant p53 shows reduced binding to the p53 response element of p21 and reduced induction of p21 mRNA in a mutant allele dose-dependent manner.

MeSH Terms
  • Alleles
  • Animals
  • Brazil
  • Carcinogenesis/genetics
  • Cell Transformation, Neoplastic/genetics
  • DNA Damage
  • Fibroblasts/metabolism
  • Gene Knock-In Techniques
  • Genetic Predisposition to Disease
  • Germ-Line Mutation
  • Homozygote
  • Humans
  • Liver/metabolism
  • Liver Neoplasms/chemically induced
  • Liver Neoplasms/pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation
  • Transcriptional Activation
  • Tumor Suppressor Protein p53/genetics
Strain GQC Summary
Gene Specific Genotyping:

To request gene-specific and other genotyping services for a strain, please contact the distribution MMRRC Center for more information.

Background Genetic Quality:

The MMRRC has developed a Genetic Quality Control pipeline using the MiniMUGA array to provide additional information to identify and validate genetic backgrounds of MMRRC strains. For more information on whether genetic background data is available, please contact MMRRC_GeneticQC@med.unc.edu. Note: that MiniMUGA genetic background data is not available on all strains, but can be ordered if desired.

Suggested Control Mice
Littermates of all relevant genotypes.
Submitter:
  • Cancer
  • Diabetes
  • Metabolism
  • Neoplastic Cell Transformation
  • Fibroblasts
  • Liver Neoplasms
  • Transcriptional Activation
  • Tumor Suppressor Protein p53
  • Modeling the human TP53 R337H germline mutation
  • Cancer susceptibility and tumorigenesis
  • Carcinogen-induced liver tumorigenesis
  • p53 tumor suppressor function
  • p53 oligomerization and transcriptional activity
  • DNA damage responses
  • Cell-cycle arrest and apoptosis
  • Li-Fraumeni syndrome-associated variant biology
Submitter
Paul Hwang, M.D., National Institutes of Health (NIH).
Primary Reference

Park JH, Li J, Starost MF, Liu C, Zhuang J, Chen J, Achatz MI, Kang JG, Wang PY, Savage SA, Hwang PM. Mouse Homolog of the Human TP53 R337H Mutation Reveals Its Role in Tumorigenesis. Cancer Res. 2018 Sep 15;78(18):5375-5383. doi: 10.1158/0008-5472.CAN-18-0016. Epub 2018 Jul 24. (Medline PMID: 30042151)

Strain Development
The Trp53 R334H knock-in strain was generated by homologous recombination in embryonic stem (ES) cells. A gene-targeting construct containing the CGC (Arg) to CAC (His) missense mutation and neomycin-resistant gene flanked by loxP sites was electroporated into PRX-B6N mES cells derived from C57BL/6NTac. G418-resistant colonies were genotyped by PCR, and two correctly targeted ES clones were injected into blastocysts collected from C57BL/6 mice. The resulting chimeras were then bred with wild-type C57BL/6 mice to confirm germline transmission (GLT) of the mutant allele. Genotype-confirmed GLT mice were crossed with CMV-Cre mice to delete the loxP-flanked neomycin resistance gene. Heterozygous mice were backcrossed to C57BL/6N for at least 5 generations.

Disclaimer: If MMRRC Strain Genetic Quality Control (GQC; based on MiniMUGA genotyping and analysis) has been completed for this strain, the information might differ from the genetic background information provided by the submitter. MiniMUGA genetic analysis is done on a strain's tissue samples taken when archived by or ordered from the assigned MMRRC Center.

Colony and Husbandry Information

For more information about this colony's health status contact csmmrrc@jax.org
Coat Color
Black
Eye
Black
MMRRC Breeding System
Backcross
Generation
5 generations
Overall Breeding Performance
Excellent
Viability and Fertility: Female Male Comments
Homozygotes are viable: Reduced Yes
Homozygotes are fertile: Yes Yes
Heterozygotes are fertile: Yes Yes
Age Reproductive Decline: 7 to 9 months Greater than 12 months
Average litter size
4 to 6
Recommended wean age
4 Weeks
Average Pups Weaned
4 to 6

Order Information

Limited quantities of breeder mice (up to 2 males and 2 females or 4 mice) per investigator per month are available from a live colony, usually available to ship in under 12 weeks. Larger quantities may be available, please contact the distributing center directly at csmmrrc@jax.org for more details.

Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.

A Commercial License Agreement from the Submitter is required for for-profit entities to use this strain. For more information, please contact Vincent Kolesnitchenko.

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

A Commercial License Agreement from the Submitter is required for for-profit entities to use this strain. For more information, please contact Vincent Kolesnitchenko

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # Description Distribution Fee / Unit (US $)
*Shipping & Handling not included*
Units Notes
076324-JAX-HET-F
076324-JAX-HET-M
Heterozygous / Hemizygous Female
Heterozygous / Hemizygous Male
$236.00 / $236.00
Non-Profit / For-Profit
Per Mouse The csmmrrc@jax.org may assess additional fees for any special requests (e.g., specific age or weight of mice, etc.).
Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.

1 The distribution fee covers the expense of rederiving mice from a live mouse; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

3 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

4 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.