COVID-19 is a serious public health threat across the globe (see Taconic's Response to COVID-19). Taconic Biosciences is proud to support preclinical research aimed at neutralizing this threat, from basic research through vaccine development. As part of this commitment, we are subsidizing distribution of specialty transgenics including humanized ACE2 mice and an Ace2 knockout mouse. See below for more details and check back frequently as we anticipate making updates to the model list.
Complimentary webinar: COVID-19 Q&A With Dr. Alessandro Sette
Note that we list research relevance based on the existing large body of research on SARS (SARS-CoV) as well as emerging reports of preclinical SARS-CoV-2 studies.
The SARS-CoV-2 spike protein binds to ACE2 on the surface of cells to facilitate entry.1,2
Mouse ACE2 is sufficiently different from human ACE2 to prevent infection by SARS-CoV-2,
meaning that wild type mice cannot be infected using clinical virus isolates. Mice
expressing human ACE2 may support infection by SARS-CoV-2 and thus be useful for studies
of vaccines, antiviral drugs and disease pathogenesis. Taconic has obtained several lines
of hACE2 transgenic mice from the lab of Chien-Te (Kent) Tseng at the University of Texas
Medical Branch.3,4 These lines were originally developed to study SARS, but may prove useful
for COVID-19 studies.
Acute respiratory distress syndrome (ARDS) is a serious complication of COVID-19 and present in a large percentage of COVID-19 deaths. ACE2 is protective against ARDS. Binding of viral spike SARS protein to ACE2 in mice downregulates ACE2 expression. Loss of ACE2 expression is associated with severe lung failure. Ace2 knockout mice have been used in ARDS and SARS research.2,5,6
The Ace2 Knockout Mouse was generated by Lexicon Pharmaceuticals and is part of Taconic's Knockout Repository under model # TF3738. It is now being distributed from a live colony under model #18180. Lexicon has generously agreed to support distribution of this model under subsidized pricing and simple terms. Taconic has recovered this model from cryopreservation and will be distributing at a subsidized cost. Quantities may be limited so that we can distribute the model to as many research groups as possible. Taconic is able to accept orders for this model now. Please visit the Ace2 Knockout model page to learn more.
Live production of the Ace2 Knockout Mouse (model #18180) is ending by Jan. 29, 2021. Please contact Taconic immediately if you would like to receive live mice prior to colony closure. The model will be available for cryorecovery in the future, but not under special pricing or terms for COVID-19/ARDS research.
TMPRSS2 is involved in SARS-CoV-2 entry into cells. Inhibition of this protein may constitute a treatment/prophylaxis mechanism. Tmprss2 knockout mice may be useful in studying COVID-19 disease pathogenesis.2,7
This model is currently cryopreserved. Please contact us if you are interested in using this model for COVID-19 research.
DPP4 is the receptor for MERS-CoV, the virus which causes Middle Eastern Respiratory Syndrome (MERS). Modeling using information from crystal structures identified DPP4 as a potential co-receptor for SARS-CoV-2; DPP4 may help facilitate entry into cells upon binding by the viral spike protein.8 Although wild type mice are not permissive for MERS infection due to differences between mouse and human DPP4, transgenic mice which express human DPP4 can be infected with MERS-CoV.9,10,11 Humanized and knockout DPP4 mice may be useful in studying COVID-19 disease pathogenesis.
Taconic has access to a humanized DPP4 mouse from the laboratory of Chien-Te (Kent) Tseng at the University of Texas Medical Branch and is developing plans to scale up and distribute this model. Please register your interest:
The human apolipoprotein E4 allele may be associated with risk of more severe COVID-19 infection and clinical outcomes compared to the E3 allele.12 APOE is involved in cholesterol transport, and the E4 allele is associated with atherosclerosis and Alzheimer's disease. APOE also plays an important immunomodulatory role and is implicated in some viral infections13, and ApoE4 is associated with heightened susceptibility to inflammation compared to ApoE2 and ApoE3 in both mice and humans.14,15
Taconic offers mice which carry human APOE alleles. Line 1549 is homozygous for the E4 allele, line 1548 is homozygous for the E3 allele, and line 1547 is homozygous for the E2 allele. Line APOE is a knockout of murine Apoe and may be a useful control for the humanized models. Taconic can produce custom hybrids which carry one E3 and one E4 allele upon request.
Stat1 knockout mice support SARS-CoV viral replication in the lungs and develop progressive lung disease including diffuse interstitial pneumonia with inflammation and systemic spread to other organs. May be useful to study disease pathogenesis and antiviral treatments.16,17,18,19
Young inbred mice such as BALB/c support viral replication of SARS and may be useful for vaccine and antiviral studies even without supporting development of disease. They may also be useful in studying immune responses to infection.19
In contrast to young mice, 12 to 14 month old BALB/c mice develop clinical illness including patchy interstitial pneumonia following SARS infection and may be useful to model the age-related mortality increase seen in humans in COVID-19.20 Taconic is holding BALB/c retired female breeders in large quantities to facilitate studies using aged mice.
As of June 5, 2020, Taconic has cohorts available between 7-11 months of age. Quantities vary, contact us for availability details.
Mouse-adapted SARS strains induce clinical illness in BALB/c mice, with similar disease characteristics as seen in humans.21
Mouse-adapted SARS-CoV-2 strains have now been reported, and inbred mice may be useful for studies of vaccines, antiviral drugs and disease pathogenesis. Mouse-adapted SARS-CoV-2 can infect and replicate in both young and aged BALB/c mice, resulting in decreased pulmonary function, mild to moderate pneumonia and inflammation.
Young inbred mice such as C57BL/6 support viral replication of SARS and may be useful for vaccine and antiviral studies even without supporting development of disease. They may also be useful in studying immune responses to infection.19
Acute respiratory distress syndrome (ARDS) is a serious complication of COVID-19 and present in a large percentage of COVID-19 deaths. C57BL/6 mice have been used in various models of acute lung injury.
Aged C57BL/6J may also be useful to study age-related mortality increases but with lower viremia compared to BALB/c.
Mouse-adapted SARS-CoV-2 strains have now been reported, and inbred mice may be useful for studies of vaccines, antiviral drugs and disease pathogenesis.22,23
Young inbred mice such as 129S6 support viral replication of SARS and may be useful for vaccine and antiviral studies even without supporting development of disease. They may also be useful in studying immune responses to infection.19
The 129S6 inbred strain is the appropriate wild type control for use with Taconic's Stat1 Knockout mice (model #2045).
Aged 129S6 may also be useful to study age-related mortality increases but with lower viremia compared to BALB/c.
Mouse-adapted SARS-CoV-2 strains have now been reported, and inbred mice may be useful for studies of vaccines, antiviral drugs and disease pathogenesis.22,23
SFB: Segmented Filamentous Bacteria may elevate the expression of coronavirus receptors in the murine small intestine.25 The Taconic Excluded Flora health standard excludes SFB, whereas the Murine Pathogen Free™ health standard tolerates SFB (note that not all Murine Pathogen Free™ locations will have SFB present). Taconic offers both B6 and BALB/c mice at both Murine Pathogen Free™ and Excluded Flora to facilitate study of this phenomenon.
Rodent temperature monitoring technology
Body temperature can be a useful clinical indicator in infectious disease mouse models, generally presenting as a drop in core body temperature.26 Although body temp data may be a useful readout for many types of studies, it is often not assessed due to measurement challenges. Implantable RFID temperature probes provide a remote tool for measuring mouse or rat body temperature following experimental infections. This provides several benefits, including: (1) the ability to monitor body temperature in real time to better quantify clinical disease course, (2) improved biosafety by maintaining animals in their cage, and (3) improved humane endpoints.
Taconic can implant RFID temperature microchips from Unified Information Devices (UID) into any mouse or rat line. Inquire for details. UID is offering a free microchip reader for qualifying purchases to support COVID-19 research.
Monoclonal and polyclonal antibodies to SARS-CoV-2 will be useful research reagents for a variety of applications. When developing a monoclonal antibody, Swiss Webster and BALB/c mice are often used for immunization and B cells harvested for fusion to myeloma cells (hybridoma). Once a monoclonal hybridoma of choice is identified, the cells may be scaled up for in vitro production or injected into mice such as BALB/c (for mouse hybridomas) or ICR scid (for mouse or xenogeneic hybridomas) for in vivo production.
Taconic BALB have been used to generate SARS-CoV-neutralizing antibodies. 27
Rationally-designed vaccine development is complicated by differences between species in the antigens presented by major histocompatibility complex (MHC) proteins. MHC is called human leukocyte antigen (HLA) in humans. The human population carries a wide variety of HLA genes which can be divided into supertypes based on similar antigen binding. Mice which carry human HLA genes are useful in vaccine discovery and development because they better model the human response to vaccines. Taconic has a portfolio of six transgenic HLA class I models designed around supertypes which give coverage for 99+% of the human population as well as one HLA Class II model.
PBMC-engrafted NOG mice (model huPBMC-NOG) have been used to study SARS vaccine response. Humanized immune system mice may be useful for studies into human immune system response to infection and/or vaccine response.28
During this difficult and overwhelming time as the COVID-19 situation continues to evolve, Taconic recognizes the need within the research community for stability and reliability. We are committed to providing you with the products and services you depend on.
Our colony management solutions can offer relief to labs and vivaria across the world that are faced with social distancing restrictions, staff reductions, or temporary closures. We are happy to provide our cryopreservation services at a highly competitive price to alleviate your worries and ensure the security of your valuable genetically modified models for the future. If you have questions about safeguarding your research animals, we suggest downloading our White Paper The Integral Role of Cryopreservation in Rodent Colony Management.
Additionally, we will continue to offer our world-renowned model generation and consultation services by leveraging the most comprehensive, fully licensed gene modification toolkit in the industry. As your lab work is likely slowing down, Taconic's PhD scientists can help you shift gears and bring to fruition a project that has been stuck on the back burner or design a model for your upcoming grant application. Let us do the work now, so you can focus on more immediate concerns for your future during these rapidly changing times.
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