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Strain Name:
C57BL/6N-Ace2em1(ACE2)MbpTmprss2em1(TMPRSS2)Mbp/Mmucd
Stock Number:
069727-UCD
Citation ID:
RRID:MMRRC_069727-UCD
Other Names:
830391, C57BL/6N-ACE2;TMPRSS2;Ace2em1Mbp/Mmucd;Tmprss2em1Mbp/Mmucd

Strain Information

Ace2em1(ACE2)Mbp
Name: angiotensin converting enzyme 2; endonuclease-mediated mutation 1, Mouse Biology Program, UC Davis
Type: Allele
Species: Multi-species
Chromosome: X
Alteration at locus: CRISPR
Tmprss2em1(TMPRSS2)Mbp
Name: transmembrane protease, serine 2; endonuclease-mediated mutation 1, Mouse Biology Program, UC Davis
Type: Allele
Species: Multi-species
Chromosome: 16
Alteration at locus: CRISPR
Ace2
Name: angiotensin converting enzyme 2
Synonyms: 2010305L05Rik
Type: Gene
Species: Mus musculus (mouse)
Chromosome: X
Alteration at locus: CRISPR
NCBI: 70008
Homologene: 41448
Tmprss2
Name: transmembrane protease, serine 2
Synonyms: epitheliasin, D16Ertd61e
Type: Gene
Species: Mouse
Chromosome: 16
Alteration at locus: CRISPR
NCBI: 50528
VEGA: 16
Homologene: 4136
Genetic Alterations

Human ACE2 DNA consisting of 5' UTR, CDS (exons 2-19) fused to mouse Ace2 3'UTR replaced the DNA region in mouse Ace2 gene stretching from the 5'UTR to the starting ATG in exon 2. The approach minimizes potential downstream splicing or RNP re-cleavage. Expression of the human CDS is primarily controlled by the mouse regulatory system and is expected to not transcribe the mouse version. Gene expression showed expected human ACE2 levels whereas mouse Ace2 was not expressed. CRISPR RNP was used to assist with homologous recombination using dsDNA repair in JM8A3 ES cells.


Human TMPRSS2 exons 3-14 (ENSG00000184012.14) was inserted in-frame into exon 2 (ENSMUSE00000641779) of the mouse Tmprss2 gene. CRISPR RNP was used to assist with homologous recombination (HR) using dsDNA repair template in ES cells. The mouse exon 2 splice acceptor and the guide protospacer (nt 1-17) were removed from the HR template to prevent potential downstream splicing or RNP re-cleavage. The expression of the human CDS is controlled by the mouse regulatory systems (including 3’UTR), and predicted to terminate with the transgene’s STOP codon without expression of the endogenous sequence. Gene expression showed expected human TMPRSS2 levels whereas mouse Tmprss2 was not expressed. CRISPR RNP was used to assist with homologous recombination using dsDNA repair template in JM8A3 ES cells derived from C57BL/6N.


ES Cell Line
JM8A3
Phenotype
In this mouse model, the expression of the mouse Ace2 and Tmprss2 genes is replaced with expression of the human ACE2 and TMPRSS2 genes. Other than expression of the human genes and inhibition of expression of the corresponding murine genes, this mouse exhibits no known observable or measurable phenotype that differs from the genetic background wildtype strain (C57BL/6N). However, it is anticipated that once exposed to SARS-CoV-2 virus (105), these mice will exhibit signs of disease that are not seen in wildtype mice.

The MMRRC also offers these related strains:

MMRRC:068346 (C57BL/6N-Ace2em1(ACE2)Mbp/Mmucd)
MMRRC:068347 (C57BL/6N-Tmprss2em1(TMPRSS2)Mbp/Mmucd)
MMRRC: 069929 (C57BL/6N-Ace2em1(ACE2)MbpTmprss2em1(TMPRSS2)MbpDpp4em1(DPP4)Mbp/Mmucd)
Strain Development
For the two alterations, CRISPR RNP was used to assist with homologous recombination (HR) using dsDNA repair template in JM8A3 ES cells. Following blastocyst injection, the chimeras were mated with C57BL/6NCrl to create germline heterozygotes. Long-range PCR products were fully sequenced; potential off-targets were absent. Subsequent backcross was to C57BL/6NCrl. The ACE2 and TMPRSS2 mouse lines were then intercrossed to create a homozygous bi-genic ACE2/TMPRSS2 mouse model.
Suggested Control Mice
C57BL/6N
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@ucdavis.edu. Older strains may not have this information.
  • Immunology and Inflammation
  • Models for Human Disease
Donor
Kent Lloyd, D.V.M., University of California, Davis.
Primary Reference
Not ready to publish

Colony and Husbandry Information

Colony Surveillance Program and Current Health Reports

For more information about this colony's health status contact mmrrc@ucdavis.edu
Coat Color
Black
Eye
Black
MMRRC Breeding System
Sib-mating
Generation
N=2
Overall Breeding Performance
Excellent
Viability and Fertility: Female Male Comments
Homozygotes are viable: Yes X-linked Ace2 hemizygous/Tmprss2 homozygous are viable
Homozygotes are fertile: Yes X-linked Ace2 hemizygous/Tmprss2 homozygous are fertile
Heterozygotes are fertile: Yes X-linked Ace2 hemizygous/Tmprss2 heterozygous are fertile
Age Reproductive Decline: Undetermined Undetermined
Average litter size
4 to 6
Recommended wean age
4 Weeks
Average Pups Weaned
4 to 6

Order Request Information

Limited quantities of breeder mice (up to 2 males and 2 females or 4 mice) per investigator per month are available from a live colony, usually available to ship in under 12 weeks. Larger quantities may be available, please contact the distributing center directly at mmrrc@ucdavis.edu for more details.

Cryopreserved material may be available upon request, please inquire to mmrrc@ucdavis.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.

A license from third party patent owner(s) may be required for for-profit entities to use mouse models derived from CRISPR-Cas9 technologies and it is the Users sole responsibility to determine whether such a license is necessary.

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
069727-UCD-M01-F
069727-UCD- M01-M
Homozygous Ace2/ACE2 & Tmprss2/TMPRSS2
Hemizygous Ace2/ACE2 & Homozygous Tmprss2/TMPRSS2
$272.50 / $674.71
Non-Profit / For-Profit
Per Mouse The mmrrc@ucdavis.edu may assess additional fees for any special requests (e.g., specific age or weight of mice, etc.).
069727-UCD-SPERM Cryo-preserved spermatozoa $546.25 / $882.81
Non-Profit / For-Profit
Aliquot Approximate quantity3
Cryopreserved material may be available upon request, please inquire to mmrrc@ucdavis.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.