Strain Name:
B6.Cg-Vhltm1.1Wkr Ndor1Tg(UBC-cre/ERT2)1Ejb/Mmnc
Stock Number:
037477-UNC
Citation ID:
RRID:MMRRC_037477-UNC
Other Names:
UBCcre; Vhl 2B/flox

Strain Information

Vhltm1.1Wkr
Name: von Hippel-Lindau tumor suppressor; targeted mutation 1.1, WK Rathmell
Synonyms: Vhl2B
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 6
Alteration at locus: Knockout
Vhl
Name: von Hippel-Lindau tumor suppressor
Synonyms: Vhlh, pVHL
Type: Gene
Species: Mouse
Chromosome: 6
Alteration at locus: Knockout
NCBI: 22346
Homologene: 465
Ndor1Tg(UBC-cre/ERT2)1Ejb
Name: transgene insertion 1, Eric J Brown
Synonyms: Cre-ER, Ubc-cre, Ubc-cre/ERT2, Tg(UBC-cre)1Ejb, UBC-CreERT2, UBC-Cre-ER-LBD-tg, CreT2, Cre-ERT2, Tg(UBC-cre/ESR1)1Ejb, Ubc-creER, Tg(UBC-cre/ERT2)1Ejb, hUBC-CreERT2, UBC-CreERT2, UBC-CreERt2
Type: Allele
Species: Multi-species
Chromosome: unknown
Alteration at locus: Transgenic (random, gene disruption)
cre/ERT2
Name: cre tamoxifen-dependent recombinase
Type: Gene
Species: Multi-species
Chromosome:
Alteration at locus: Transgenic (random, gene disruption)
Ndor1
Name: NADPH dependent diflavin oxidoreductase 1
Synonyms: NR1, 4930447P04Rik
Type: Gene
Species: Mouse
Chromosome: 2
Alteration at locus: Transgenic (random, gene disruption)
NCBI: 78797
Homologene: 7144
UBC
Name: ubiquitin C
Type: Gene
Species: Homo sapiens (human)
Chromosome: 12
Alteration at locus: Transgenic (random, gene disruption)
Genetic Alterations
Vhl exons 2 and 3 were cloned into the targeting vector. Site-directed mutagenesis at position 398 (G-to-A conversion), in exon 3 predicts a change in codon 133, replacing an arginine with glutamine. A floxed neomycin cassette was inserted in intron 2 as well.

HGVS nomenclature:
  • Genbank RefSeq - mRNA: NM_009507.4
  • Genbank RefSeq, protein: NP_033533.1
  • Variant, nucleic acid level: c.398G>A
  • Variant, amino acid level, predicted: p.Arg133Gln
  • Notes: The initial description of this variant read "... 518 (G to A conversion), in exon 3 causes a change in codon 167". Based on Fig. 1A in PMID:19252526, this was corrected.
    Check this variant: LUMC Mutalyzer
The Cre-ERT2 transgenic mouse line was generated via lentitransgenesis; a self-inactivating lentiviral vector was designed with the human ubiquitin C (UBC) promoter sequence upstream of a Cre-ERT2 fusion gene (Cre recombinase fused to a G400V/M543A/L544A triple mutation of the human estrogen receptor ligand-binding domain). Cre-ERT2-expressing lentivirus was microinjected into the perivitelline space of one-cell zygotes (129SvEv;C57BL/6 mixed genetic background). Mice display tamoxifen-inducible Cre activity in all tissue types. Line 1 inserted into the gene at 25,249,816-25,249,821 (Build GRCm38/mm10) resulting in a 5-bp deletion.
Genotype Determination
  • Genotyping Protocol(s)
  • Center protocol and contact for technical support will be shipped with mice.
  • ES Cell Line
    J1 derived from 129S4/SvJae
    Phenotype

    Homozygous: Embryonic lethal at E9.5-E10.5 due to a vascular defect in the placenta attachment to the maternal vasculature.

    Heterozygous: Wild-type in appearance, except for an over-grooming phenotype leading to bald spots in older mice. These mice breed normally.

    Mammalian Phenotype Terms
    Allelic Composition: Vhltm1.1Wkr/Vhltm1.1Wkr (Genetic Background: involves: 129S4/SvJae * C57BL/6 )

    Allelic Composition: Vhltm1.1Wkr/Vhl+ (Genetic Background: involves: 129S4/SvJae * C57BL/6 )

    MeSH Terms
    • Animals
    • Basic Helix-Loop-Helix Transcription Factors/physiology
    • Cell Line
    • Female
    • Humans
    • Hypoxia-Inducible Factor 1, alpha Subunit/physiology
    • Kidney Neoplasms/etiology
    • Mice
    • Mice, Inbred C57BL
    • Mutation
    • Teratoma/blood supply
    • Teratoma/pathology
    • Von Hippel-Lindau Tumor Suppressor Protein/genetics
    Strain Development
    For the Vhl knockout, correctly targeted J1 ES cells (129S4/SvJae; transiently transfected with Cre to remove neo) were injected into C57BL/6 blastocysts. The resulting chimeras were crossed to C57BL/6 females and mated, for several generations, to a B6-based Cre deleter line expressing Tg(EIIa-cre)C5379Lmgd (PMID:10681148), which adds an FVB background component due to the development of the Cre allele. This was followed by backcrossing to C57BL/6. The line was then crossed to combine with the UBC-cre/ERT2 allele (e.g., JAX Strain #007001) and, finally, backcrossed to C57BL/6 to N8.
    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
    • Models of Human Diseases (von Hippel-Lindau disease Type 2B)
    Donor
    W. Kimryn Rathmell, M.D., University of North Carolina at Chapel Hill.
    Primary Reference

    Lee CM, Hickey MM, Sanford CA, McGuire CG, Cowey CL, Simon MC, Rathmell WK. VHL Type 2B gene mutation moderates HIF dosage in vitro and in vivo. Oncogene. 2009 Apr 9;28(14):1694-705. (Medline PMID: 19252526)

    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
    Agouti
    Eye
    Black
    MMRRC Breeding System
    Backcrossing and random intra-strain mating
    Breeding Scheme(s)
    • Wild-type female x Heterozygous male from the colony or reciprocal mating
    • Heterozygous female x Heterozygous male from the colony
    Generation
    N8 (C57BL/6J)
    Overall Breeding Performance
    Good
    Viability and Fertility: Female Male Comments
    Homozygotes are viable: No No
    Homozygotes are fertile: No No
    Heterozygotes are fertile: Yes Yes
    Age Reproductive Decline: 10 months >12 months
    Average litter size
    5-9
    Recommended wean age
    3-4 weeks
    Average Pups Weaned
    5-9

    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
    037477-UNC-EMBRYO Cryo-preserved embryos $1,404.00 / Non-Profit Aliquot Approximate quantity2 : 20-40 embryos / aliquot
    037477-UNC-SPERM Cryo-preserved spermatozoa $564.00 / Non-Profit Aliquot Approximate quantity3
    037477-UNC-RESUS Litter recovered from cryo-archive $2,914.00 / Non-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.