Strain Name:
B6.129-Mdm2tm2.1Ypz/Mmnc
Stock Number:
042097-UNC
Citation ID:
RRID:MMRRC_042097-UNC
Other Names:
Mdm2-Y487A knock-in ,

Strain Information

Mdm2tm2.1Ypz
Name: transformed mouse 3T3 cell double minute 2; targeted mutation 2.1, Yanping Zhang
Synonyms: Mdm2Y487A
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 10
Alteration at locus: Targeted Mutation
Mdm2
Name: transformed mouse 3T3 cell double minute 2
Synonyms: Mdm-2, 1700007J15Rik
Type: Gene
Species: Mouse
Chromosome: 10
Alteration at locus: Targeted Mutation
NCBI: 17246
HGNC: HGNC:6973
Homologene: 1793
Genetic Alterations
A Tyr-to-Ala substitution (TAC to GCA) was introduced in codon 487 of Mdm2 gene.
Genotype Determination
  • Genotyping Protocol(s)
  • Center protocol and contact for technical support will be shipped with mice.
  • ES Cell Line
    AB2.2
    Phenotype

    Homozygous: Mdm2Y487A/Y487A homozygous mice were observed at normal and fertile. When Mdm2Y847A/Y487A homozygous mice were treated with a sublethal dose (5 Gy) of γ IR, resulted in significant weight loss and 100% lethality by 22 days post treatment.

    Heterozygous: Mice heterozygous for Mdm2Y487A were viable, and appeared phenotypically normal and fertile.

    MeSH Terms
    • Animals
    • DNA Damage
    • DNA Repair
    • Embryonic Development/genetics
    • Female
    • Male
    • Mice
    • Mice, Inbred C57BL
    • Mice, Transgenic
    • Mutation, Missense
    • Organ Specificity
    • Protein Binding
    • Protein Multimerization
    • Proteolysis
    • Proto-Oncogene Proteins c-mdm2/genetics
    • Proto-Oncogene Proteins c-mdm2/metabolism
    • Radiation Tolerance/genetics
    • Tumor Suppressor Protein p53/metabolism
    • Ubiquitination
    Strain Development
    The targeting vector was constructed in a PGK neo vector described (Itahana et al., 2007). A Tyr-to-Ala substitution (TAC to GCA) was introduced in codon 487 of Mdm2 using site-directed mutagenesis. The final construct was confirmed by sequenced using overlapping primers. Electroporation of 129/Sv-derived AB2.2 ES cells was performed by the UNC Animal Models Core Facility. DNA isolated from G418-resistant ES colonies were confirmed for the presence of the Y487A substitution by PCR amplification of genomic DNA using primers flanking exon 12, followed by sequencing. The positive clones were injected into C57BL/6 blastocysts, and the blastocysts were transferred into pseudopregnant female recipients. The resulting chimeric males were mated with C57BL/6 females; germline transmission was confirmed by PCR analysis and DNA sequencing. Following germline transmission of the Mdm2Y487A mutation, Mdm2Y487A/+ mice were mated with Ella-Cre transgenic mice (Jackson Laboratories, stock number 003724) to excise the neomycin selection marker. The resulting mice were backcrossed to C57BL/6 (Jackson Laboratories, stock number 000664) for nine generations. Mice were bred and maintained strictly under protocols 13–044 approved by the Institutional Animal Care and Use Committee at the University of North Carolina at Chapel Hill Animal Care Facility.
    Suggested Control Mice
    Wild-type littermates
    MMRRC Genetic QC Summary
    The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact mmrrc@med.unc.edu. Older strains may not have this information.
    • Cancer
    • Cell Biology
    Donor
    Zhang [Ph.D.], Yanping
    Primary Reference

    Laura A. Tollini, Aiwen Jin, Jikyoung Park, Yanping Zhang. Regulation of p53 by Mdm2 E3 Ligase Function is Dispensable in Embryogenesis and Development but Essential in Response to DNA Damage. Cancer Cell. 2014 Aug 11;26(2):235-47. (Medline PMID: 25117711)

    Colony and Husbandry Information

    Colony Surveillance Program and Current Health Reports

    Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc_health@med.unc.edu.
    Coat Color
    Black.
    MMRRC Breeding System
    Backcross
    Generation
    Nine.
    Overall Breeding Performance
    Good
    Viability and Fertility: Female Male Comments
    Homozygotes are viable: Yes Yes
    Homozygotes are fertile: Yes Yes
    Heterozygotes are fertile: Yes Yes
    Age Reproductive Decline: 6 to 8 months 8 to 12 months
    Average litter size
    4-6
    Recommended wean age
    3 weeks

    Order Request Information

    Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

    Cryopreserved material may be available upon request, please inquire to mmrrc@med.unc.edu for more information.

    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.

    The donor or their institution limits the distribution to non-profit institutions only.

    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
    042097-UNC-RESUS Litter recovered from cryo-archive $2,914.00 / Non-Profit Litter Recovered litter4; additional fees for any special requests.
    Cryopreserved material may be available upon request, please inquire to mmrrc@med.unc.edu 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.