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Strain Name:
B6.Cg-Tg(Igh-2-12Vh/Ighma)1Shc Tg(IgkH220-17)1Mwg/Mmnc
Stock Number:
031069-UNC
Citation ID:
RRID:MMRRC_031069-UNC

Strain Information

Igk
Name: immunoglobulin kappa chain complex
Synonyms: kappa
Type: Complex/Cluster/Region
Species: Mus musculus (mouse)
Chromosome: 6
Alteration at locus: Transgenic
Igh
Name: immunoglobulin heavy chain complex
Type: Complex/Cluster/Region
Species: Mus musculus (mouse)
Chromosome: 12
Alteration at locus: Transgenic
Tg(IgkH220-17)1Mwg
Name: transgene insertion 1, Martin Weigert
Synonyms: Tg(IgK-V8, IgK-J5)1Tnm, Vkappa8 Tg
Type: Transgene
Species: Mus musculus (mouse)
Chromosome: unknown
Alteration at locus: Transgenic
Tg(Igh-2-12Vh/Ighma)1Shc
Name: transgene insertion 1, Stephen Clarke
Synonyms: 2-12H Tg, Tg(Igh-V2-12H/Igh-6)1Shc, IgSm
Type: Transgene
Species: Mus musculus (mouse)
Chromosome: unknown
Alteration at locus: Transgenic
Genetic Alterations
This mouse expresses an IgM heavy chain specific for the Smith autoantigen and a restricted Vk8 light chain. All B cells in this mouse are autoreactive, however the B cells are maintained in a state of tolerance and do not produce autoantibody.
Genotype Determination
  • Genotyping Protocol(s)
  • Center protocol and contact for technical support will be shipped with mice.
  • Phenotype
    Homozygous: Undetermined.

    Hemizygous: Increased prelevance of autoimmune disease compared to MRL mice endogenous Ig expression.This mouse provides a model where B cells specific for a defined autoantigen are expressed, but the autoreactive B cells are tolerized such that no autoantibody is produced. The antigen this B cells recognize, Smith antigen (Sm), has been shown to be involved in both human and murine Systemic Lupus Erythematosus (SLE). Since the B cells in this mice are autoreactive but the mice do not develop disease pathology, they provide a model to study autoreactive B cell regulation.

    MeSH Terms
    • Amino Acid Sequence
    • Animals
    • Autoantibodies/chemistry
    • Autoantibodies/genetics
    • Autoantigens/immunology
    • Base Sequence
    • Clone Cells
    • Gene Rearrangement, B-Lymphocyte, Heavy Chain
    • Gene Rearrangement, B-Lymphocyte, Light Chain
    • Genes, Immunoglobulin
    • Hybridomas
    • Immunoglobulin kappa-Chains/genetics
    • Lupus Erythematosus, Systemic/immunology
    • Mice
    • Mice, Mutant Strains
    • Molecular Sequence Data
    • Mutation
    • Ribonucleoproteins, Small Nuclear
    • Sequence Alignment
    • snRNP Core Proteins
    • Antibody Affinity
    • Autoantigens/genetics
    • B-Lymphocyte Subsets/classification
    • B-Lymphocyte Subsets/immunology
    • Cell Differentiation
    • Cells, Cultured
    • Clonal Anergy
    • Histocompatibility Antigens Class II/metabolism
    • Immunoglobulin M/blood
    • Immunophenotyping
    • Kinetics
    • Mice, Inbred MRL lpr
    • Mice, Transgenic
    • Receptors, Antigen, B-Cell/immunology
    • Spleen/immunology
    • fas Receptor/metabolism
    • Antibodies, Viral/genetics
    • Antibody Formation
    • Blotting, Northern
    • Blotting, Southern
    • Cloning, Molecular
    • Gene Expression
    • Hemagglutinins, Viral/immunology
    • Hemocyanins/immunology
    • Immunoglobulin Variable Region/genetics
    • Influenza A virus/immunology
    • Lipopolysaccharides/immunology
    • Mice, Transgenic/immunology
    • Oligonucleotides/chemistry
    • RNA, Messenger/genetics
    • Restriction Mapping
    • Transcription, Genetic
    • B-Lymphocytes/immunology
    • Bone Marrow/immunology
    • DNA, Single-Stranded/immunology
    • Enzyme-Linked Immunosorbent Assay
    • Fluorescent Antibody Technique
    • Hematopoietic Stem Cells
    • Immune Tolerance
    • Lupus Erythematosus, Systemic/etiology
    • Lymphocyte Activation
    • Ribonucleoproteins, Small Nuclear/immunology
    Strain Development

    Transgenic (Tg) 2-12H mice were engineered by incorporating the rearranged V(D)J segment derived from the 2-12H hybridoma. This variable immunoglobulin gene segment was cloned upstream of the Igha constant region (Cu) gene. The purified DNA construct was microinjected into blastocysts from (C57BL/6 × SJL)F1 crosses, which were subsequently implanted into pseudopregnant females. Two transgenic founder lines were established and backcrossed to either C57BL/6 or C.B-17 mice for a minimum of eight generations. The mixed-origin line has since been further backcrossed to C57BL/6 for thirteen generations. Transgene transmission was confirmed via polymerase chain reaction (PCR) analysis of tail DNA, utilizing a forward oligonucleotide primer (5'-CAGACTAAGGCCAAATATCAACTGAGAGA-3') matching a sequence 470 base pairs (bp) upstream of the 2-12 Vh exon and a reverse primer (5'-CAGGCTCCACCAGACCTCTCTAGA-3') complementary to a sequence downstream of Jh4.

    Transgenic Vk8 mice were generated by microinjection of cloned functionally rearranged Vk8 L chain gene DNA into (C57BL/6 x SJL) F1 x F1 zygotes and transferred into pseudopregnant ICR/Halcr females. Inbred lines were established by backcrossing founder mice to BALB/c mice for six or more generations. The BALB/c background have been backcrossed to C57BL/6 thirteen generations. Mice containing the transgene were identified by polymerase chain reaction analysis of tail DNA using an oligonucleotide complementary to the Vk8 leader (5'-GGTACCTGTGGGACATTGTG- 3') and an oligonucleotide specific to the Vk8/Jk5 junction (5'- AGCACCGAACGTGAGAGG-3').

    Mice containing the 2-12H transgene and mice containing the Vk8 transgene were bred to produce mice with both transgenes, referred to as 2-12h/Vk8 Tg mice.

    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.
    • Immunology and Inflammation
    • Models for Human Disease
    • Research Tools
    Donor
    Barbara Vilen, Ph.D., University of North Carolina at Chapel Hill
    Primary Reference
    • Bloom DD; Davignon JL; Retter MW; Shlomchik MJ; Pisetsky DS; Cohen PL; Eisenberg RA; Clarke SH, V region gene analysis of anti-Sm hybridomas from MRL/Mp-lpr/lpr mice., J Immunol 1993 Feb 15;150(4):1591-610 (Medline PMID: 8432995)
    • Borrero M; Clarke SH, Low-affinity anti-Smith antigen B cells are regulated by anergy as opposed to developmental arrest or differentiation to B-1., J Immunol 2002 Jan 1;168(1):13-21 (Medline PMID: 11751941)
    • Carmack CE; Camper SA; Mackle JJ; Gerhard WU; Weigert MG, Influence of a V kappa 8 L chain transgene on endogenous rearrangements and the immune response to the HA(Sb) determinant on influenza virus., J Immunol 1991 Sep 15;147(6):2024-33 (Medline PMID: 1909739)
    • Santulli-Marotto S; Retter MW; Gee R; Mamula MJ; Clarke SH, Autoreactive B cell regulation: peripheral induction of developmental arrest by lupus-associated autoantigens., Immunity 1998 Feb;8(2):209-19 (Medline PMID: 9492002)

    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
    Eye
    Black
    MMRRC Breeding System
    Backcross or Intra-strain Random Mating.
    Generation
    N13
    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:
    Homozygotes are fertile:
    Hetero/Hemizygotes are fertile:
    Age Reproductive Decline: 10 months 10 months
    Average litter size
    8
    Recommended wean age
    3 Weeks
    Average Pups Weaned
    8

    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
    031069-UNC-RESUS Litter recovered from cryo-archive $3,088.00 / 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.