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Strain Detail Sheet

Strain Name:
B6J.Cg-Tg(FOXJ1-ACE2)1Rba/Mmnc
Stock Number:
066719-UNC
Citation ID:
RRID:MMRRC_066719-UNC
Other Names:
HFH4-ACE2

Strain Information

Gene Details

Tg(FOXJ1-ACE2)1Rba
Name:
Type: Allele
Species: Homo sapiens (human)
Chromosome:
ACE2
Name: angiotensin I converting enzyme 2
Type: Gene
Species: Homo sapiens (human)
Chromosome: X
FOXJ1
Name: forkhead box J1
Type: Gene
Species: Homo sapiens (human)
Chromosome: 17
Genetic Alterations
These mice express human angiotensin-converting enzyme-2 (ACE2) in various tissues, under the control of human HFH4 (FOXJ1); a lung ciliated epithelial cell promoter.

Note:

To map the Tg insertion site and facilitate genotyping, the MMRRC generated a whole-genome sequence of the MMRRC founder transgenic male at 50x coverage using Novaseq of a genomic library of 150bp paired-end reads. Using these data, the MMRRC:

  1. Extracted the genomic sequence of the transgene. The 5kb sequence matches the description of the transgene in the original paper (PMID:26976607).
  2. Estimated the copy number in the founder male. The transgene copy number is in the 50 to 70 range.
  3. Given the large number of copies, the donor determined the co-orientation of some of these copies. This analysis indicates that, in addition to head-to-tail, there are head-to-head and tail-to-tail configurations.
  4. Identified one insertion site of the transgene in chromosome 13 at 70,588,516. This insertion site appears to involve substantial genomic rearrangement.
Genotype Determination
  • Genotyping Protocol(s)
  • Center protocol and contact for technical support will be shipped with mice.

    • Strain Description

    Phenotype
    Robust expression was observed in the lungs; other tissues including the brain, liver, kidney, and gastrointestinal tract had varying levels of human ACE2 expression, indicating greater tissue distribution of HFH4(FOXJ1)-mediated expression than initially expected (see PMID:26976607, Fig. S3). This mouse is particularly susceptible to severe acute respiratory distress syndrome coronavirus (SARS-CoV) including the epidemic non-mouse adapted strain. Transgene expression in the lung of the MMRRC founder was confirmed by the MMRRC-UNC (RT-PCR, data available upon request).
    MeSH Terms
    • Animals
    • Antibodies, Monoclonal/immunology
    • Antibodies, Neutralizing/immunology
    • Antibodies, Viral/immunology
    • Cells, Cultured
    • Chiroptera/virology
    • Chlorocebus aethiops
    • Communicable Diseases, Emerging/virology
    • Coronaviridae/genetics
    • Coronaviridae/immunology
    • Coronaviridae/isolation & purification
    • Coronaviridae/pathogenicity
    • Coronaviridae/physiology
    • Coronaviridae Infections/prevention & control
    • Coronaviridae Infections/transmission
    • Coronaviridae Infections/veterinary
    • Coronaviridae Infections/virology
    • Cross Reactions
    • Encephalitis, Viral/virology
    • Epithelial Cells/virology
    • Host Specificity
    • Humans
    • Lung/cytology
    • Mice
    • Mice, Inbred BALB C
    • Mice, Transgenic
    • Models, Molecular
    • Peptidyl-Dipeptidase A/genetics
    • Peptidyl-Dipeptidase A/physiology
    • Point Mutation
    • Protein Conformation
    • Receptors, Virus/genetics
    • Receptors, Virus/physiology
    • Recombinant Fusion Proteins/metabolism
    • SARS Virus/immunology
    • Species Specificity
    • Spike Glycoprotein, Coronavirus/genetics
    • Spike Glycoprotein, Coronavirus/physiology
    • Vero Cells
    • Virus Replication
    • Zoonoses
    Strain Development

    Transgenic mice with airway-targeted overexpression of human ACE2 were generated by microinjection of fertilized (C3H x C57BL/6)F1 (C3B6F1) hybrid oocytes with an expression cassette consisting of the human HFH4 (FOXJ1) lung ciliated epithelial cell-specific promoter and the coding region of ACE2 cDNA in a pTG1 vector. Founder line #1 was crossed to C3B6F1 mice producing human ACE2-transgenic mice, and subsequent progeny were backcrossed for 25+ generations to C57BL/6J.

    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

    • Models for Human Disease
    • Virology

    Strain Origin

    Donor
    Ralph Baric, Ph.D., The University of North Carolina.
    Primary Reference

    Menachery VD, Yount BL Jr, Sims AC, Debbink K, Agnihothram SS, Gralinski LE,Graham RL, Scobey T, Plante JA, Royal SR, Swanstrom J, Sheahan TP, Pickles RJ,Corti D, Randell SH, Lanzavecchia A, Marasco WA, Baric RS. SARS-like WIV1-CoVpoised for human emergence. Proc Natl Acad Sci U S A. 2016 Mar15;113(11):3048-53. doi: 10.1073/pnas.1517719113. Epub 2016 Mar 14. (Medline PMID: 26976607)

    Additional References

    Jiang RD, Liu MQ, Chen Y, Shan C, Zhou YW, Shen XR, Li Q, Zhang L, Zhu Y, Si HR, Wang Q, Min J, Wang X, Zhang W, Li B, Zhang HJ, Baric RS, Zhou P, Yang XL, Shi ZL. Pathogenesis of SARS-CoV-2 in Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2. Cell. 2020 Jul 9;182(1):50-58.e8. doi: 10.1016/j.cell.2020.05.027. Epub 2020 May 21. (Medline PMID: 32516571)

    Colony and Husbandry Information

    Special Considerations


    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
    Generation
    N25+ (C57BL/6J)
    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: Undetermined Undetermined
    Homozygotes are fertile: Yes Yes
    Hetero/Hemizygotes are fertile: Yes Yes
    Age Reproductive Decline: 7 to 9 months 10 to 12 months
    Average litter size
    4 to 6
    Recommended wean age
    3 Weeks
    Average Pups Weaned
    4 to 6

    Order Request Information

    Availability Level

    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 Jacqueline Quay.

    Conditions of Distribution

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

    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.

    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
    066719-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.