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Strain Detail Sheet

Strain Name:
C57BL/6J-Tnfrsf11bem1Xulab/Mmnc
Stock Number:
071379-UNC
Citation ID:
RRID:MMRRC_071379-UNC
Other Names:
opg-AAA

Strain Information

Gene Details

Tnfrsf11bem1Xulab
Name: tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin); endonuclease-mediated mutation 1, Ding Xu
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 15
Alteration at locus: Knock-In
Tnfrsf11b
Name: tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin)
Synonyms: osteoclastogenesis inhibitory factor, OCIF, OPG, Opg, TR1
Type: Gene
Species: Mouse
Chromosome: 15
Alteration at locus: Knock-In
NCBI: 18383
VEGA: 15
Homologene: 1912

Additional Resources
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KOMP Phenotyping
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GeneCards
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Genetic Alterations
Triple nonsynonymous nucleotide substitutions located at exon 5 of the C-terminal tail domain of Tnrfsf11b (opg) were generated using CRISPR/Cas9-based targeting and homology-directed repair. Synthesized small guided RNAs (sgRNAs), repair template ssODN, and messenger RNA encoded for CRISPR-associated protein 9 (Cas9) were microinjected into one cell-stage fertilized egg to obtain the targeted knock-in mutations, R336A, K367A, and R370A.


Genotype Determination
  • Genotyping Protocol(s)
  • Center protocol and contact for technical support will be shipped with mice.
    • ES Cell Line
    Not applicable

    Strain Description

    Phenotype

    This knock-in mouse strain grew normally without gross morphological abnormalities. The primary phenotype of this mouse strain displayed an osteoporotic phenotype. This phenotype, as described in PMID32636266, resulted from targeted triple mutations at the C-terminal tail locus of OPG, ultimately preventing the crucial binding between OPG and heparan sulfate (HS). Thus, the HS Binding-Deficient OPG becomes incapable of producing antiresorptive activity for bone remodeling


    MeSH Terms
    • Animals
    • Binding Sites
    • Bone Density Conservation Agents/metabolism
    • Bone Density Conservation Agents/pharmacology
    • Bone Resorption/metabolism
    • Bone Resorption/pathology
    • Bone and Bones/metabolism
    • Cell Line
    • Disease Models, Animal
    • Female
    • Heparitin Sulfate/metabolism
    • Male
    • Mice
    • Mice, Inbred C57BL
    • Mice, Knockout
    • Osteoblasts/metabolism
    • Osteoclasts/metabolism
    • Osteogenesis/genetics
    • Osteogenesis/physiology
    • Osteoporosis/genetics
    • Osteoporosis/metabolism
    • Osteoporosis/pathology
    • Osteoprotegerin/genetics
    • Osteoprotegerin/metabolism
    • Osteoprotegerin/pharmacology
    • RANK Ligand/metabolism
    • Transcriptome
    Strain Development
    CRISPR guide(s) and Cas9 protein were microinjected into C57BL/6J zygotes and progeny were screened for the desired mutation. Founders were mated to C57BL/6J breeders (Jackson stock 000664), and derived N1 progeny were identified by PCR and/or sequencing. N1 were then mated again to C57BL/6J breeders to generate N2 mice identified by PCR and/or sequencing. N2 heterozygous mutant mice were mated for production of phenotyping cohorts, and N2 or N2F1 mice were used for cryopreservation purposes.
    Suggested Control Mice
    C57BL/6J

    MMRRC Genetic QC

    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.

    Research Applications

    • Cardiovascular
    • Cell Biology
    • Metabolism

    Strain Origin

    Donor
    Ding Xu, Ph.D., University at Buffalo.
    Primary Reference

    Li M, Xu D. Antiresorptive activity of osteoprotegerin requires an intact heparan sulfate-binding site. Proc Natl Acad Sci U S A. 2020 Jul 21;117(29):17187-17194. doi: 10.1073/pnas.2005859117. Epub 2020 Jul 7. (Medline PMID: 32636266)

    Colony and Husbandry Information

    Special Considerations

    N/A

    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
    Sib-mating
    Generation
    N/A
    Overall Breeding Performance
    Good

    Reproductive Statistics

    Viability and Fertility: Female Male Comments
    Homozygotes are viable: Yes Yes
    Homozygotes are fertile: Yes Yes
    Heterozygotes are fertile: Yes Yes
    Age Reproductive Decline: 7 to 9 months 10 to 12 months
    Bred to Homozygosity
    Yes
    Average litter size
    7 to 9
    Recommended wean age
    3 Weeks
    Average Pups Weaned
    7 to 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 Licensing Administrator.

    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 Licensing Administrator

    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
    071379-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.
    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.