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Strain Detail Sheet

Strain Name:
B6(Cg)-Cdkn2atm4Nesh/Mmnc
Stock Number:
043539-UNC
Citation ID:
RRID:MMRRC_043539-UNC
Other Names:
p16INK4a-tdTomato, p16-tdTomato, p16-tdTom, p16-Tomato, p16INK4a-Tomato

Strain Information

Gene Details

Cdkn2atm4Nesh
Name: cyclin dependent kinase inhibitor 2A; targeted mutation 4, Norman E Sharpless
Synonyms: p16tdTOM
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 4
Alteration at locus: Knock-In
Cdkn2a
Name: cyclin dependent kinase inhibitor 2A
Synonyms: MTS1, p19ARF, p16INK4a, INK4a-ARF, p16, ARF-INK4a, Arf, Pctr1, p19ARF, Ink4a/Arf
Type: Gene
Species: Mouse
Chromosome: 4
Alteration at locus: Knock-In
NCBI: 12578
HGNC: HGNC:1787
Homologene: 55430

Additional Resources
IMPC
Google
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Gene Ontology
BioGPS
Gene Cloud
IGTC
Mouse Phenome DB
Mouse Mine
KOMP Phenotyping
Monarch
GeneCards
ClinGen
tdTomato
Name:
Type: Gene
Species: Discosoma sp. (mushroom coral)
Chromosome:
Alteration at locus: Knock-In
Genetic Alterations
Exon1(alpha) was replaced with a translation start site followed by tdTomato cDNA, an SV40 polyadenylation signal, and a FRT-flanked neo cassette. The neo cassette was retained, as it proved to enhance tdTomato expression. It may be removed via Flp-mediated recombination.
Genotype Determination
  • Genotyping Protocol(s)
  • Center protocol and contact for technical support will be shipped with mice.
    • ES Cell Line
    v6.5 derived from (C57BL/6 x 129S4/SvJae)F1

    Strain Description

    Phenotype

    Homozygous: Mostly normal phenotype. Mice have cancer-prone phenotype with aging, causing reduced lifespan, as null for p16INK4a expression so similar to p16 KO (PMID:11544531). Express tdTomato. No known embryonic lethality.

    Hetero/Hemizygous: Normal phenotype. Express tdTomato. No known embryonic lethality.

    MeSH Terms
    • Animals
    • Cell Proliferation
    • Cellular Senescence/genetics
    • Cyclin-Dependent Kinase Inhibitor p16/genetics
    • Enzyme Activation
    • Fibroblasts/metabolism
    • Half-Life
    • Humans
    • Mice
    • Phenotype
    • Promoter Regions, Genetic
    • RNA, Messenger/genetics
    • beta-Galactosidase/metabolism
    Strain Development
    The allele was targeted in v6.5 hybrid ES cells derived from (C57BL/6 x 129S4/SvJae)F1.Backcrossed to C57BL/6J (JAX Strain #000664) eight times.
    Suggested Control Mice
    Wild-type littermates

    MMRRC Genetic QC

    MMRRC Genetic QC Summary
    Genetic QC analysis (GQC) was performed on representative samples from the donor submission and provides a baseline reference. Regardless of the material ordered (live mice, sperm, embryos, resuscitated animals), the provided material is guaranteed to contain the primary genetic alteration of interest; however, the composition of the genetic background may vary (See Reproducibility sections of the report for details). The impact of genetic background on previously reported phenotypes has not been evaluated.

    GQC analysis was done on two samples NA6730 (XX), WW1510 (XY) at the time of importation and the conclusions are consistent in both samples - both are not inbred and contain multiple C57BL/6 substrains. The results of the analysis are not congruent with the SDS (see special considerations and details below) and WW1510 is the representative sample selected for the report. The primary (host) background is C57BL/6J and there is positive evidence of C57BL/6J and C57BL/6N substrains. The secondary (donor) background is consistent with 129S4, which is indicated in the submission and the SDS as the donor strain (B6J/129S4 F1 ES Cells). The Y chromosome is consistent with at least one backcross to a male from the host background (C57BL/6J substrain). The mitochondrial genome is consistent with at least one backcross to a female from the host background (either the C57BL/6J or C57BL/6N substrain). The region containing the allele of interest has the 129S4 donor background. Therefore, the targeting event was on the 129S4 chromosome of the F1 ES cells. One sample is heterozygous and one sample is homozygous for the donor background at the locus. The following constructs are detected in both samples: hTK_Pr and r_FP.

    The genome of the MMRRC: 43539 strain is 87.4% inbred and 89.6% congenic at the strain level. Donor contribution in the linked interval spans 73.3MB. The level of congenicity estimated by miniMUGA is inconsistent with the number of backcross generations reported in the SDS (8 generations). 71.2% of the genome is segregating for the two substrains (C57BL/6J and C57BL/6N) that contribute to the primary (host) background. The contribution of the C57BL/6J substrain is 59.3.X%. The contribution of the C57BL/6N substrain is 34%.

    The estimated inbreeding, congenicity, and the relative strain/substrain contribution depend on the number of samples genotyped. The genomes of strains that are not fully inbred are not completely reproducible.
    MiniMUGA Sample Report
    MiniMUGA Sample Report Link

    Research Applications

    • Cancer
    • Cell Biology
    • Dermatology
    • Hematology
    • Immunology and Inflammation
    • Models for Human Disease

    Strain Origin

    Donor
    Norman Sharpless, M.D., University of North Carolina at Chapel Hill.
    Suresh Kumar, Ph.D., NIH - National Institute of Aging.
    Primary Reference

    Liu JY, Souroullas GP, Diekman BO, Krishnamurthy J, Hall BM, Sorrentino JA,Parker JS, Sessions GA, Gudkov AV, Sharpless NE. Cells exhibiting strong p16(INK4a) promoter activation in vivo display features of senescence. Proc NatlAcad Sci U S A. 2019 Feb 12;116(7):2603-2611. doi: 10.1073/pnas.1818313116. Epub 2019 Jan 25. (Medline PMID: 30683717)

    Colony and Husbandry Information

    Health Status Report

    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.

    Appearance

    Coat Color
    Black
    Eye
    Black

    Breeding

    MMRRC Breeding System
    Backcross and sib-mating
    Breeding Scheme(s)
    p16 tdTomato/tdTomato homozygous x homozygous
    Generation
    N8 (C57BL/6J), F10+
    Overall Breeding Performance
    Good

    Reproductive Statistics

    NOTE: "Hemizygote" as used here refers to males carrying a mutation on the X Chromosome or mice of either sex carrying an inserted transgene with no homologous allele on the other chromosome.
    Viability and Fertility: Female Male Comments
    Homozygotes are viable: Yes Yes
    Homozygotes are fertile: Yes Yes
    Hetero/Hemizygotes are fertile: Yes Yes
    Age Reproductive Decline: 6 to 8 months 8 to 12 months
    Bred to Homozygosity
    No
    Average litter size
    5-9
    Recommended wean age
    3-4 weeks
    Average Pups Weaned
    5-9

    Order Request Information

    Availability Level

    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.

    A Commercial License Agreement from the Donor is required for for-profit entities to use this strain. For more information, please contact Carmen Melvin.

    Conditions of Distribution

    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 Donor is required for for-profit entities to use this strain. For more information, please contact Carmen Melvin

    Fees

    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
    043539-UNC-EMBRYO Cryo-preserved embryos $1,488.00 / $2,470.00
    Non-Profit / For-Profit    		 Aliquot Approximate quantity2 : 20-40 embryos / aliquot
    043539-UNC-SPERM Cryo-preserved spermatozoa $520.00 / $863.00
    Non-Profit / For-Profit    		 Aliquot Approximate quantity3
    043539-UNC-RESUS Litter recovered from cryo-archive $3,088.00 / $5,126.00
    Non-Profit / For-Profit    		 Litter Recovered litter4; additional fees for any special requests.

    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.