Taconic Biosciences' Coronavirus (COVID-19) Toolkit

Taconic Biosciences' Coronavirus (COVID-19) Toolkit COVID-19 is a serious public health threat across the globe. 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 an Ace2 knockout mouse. We are additionally providing discounts on other key models to facilitate this important research. See below for more details and check back frequently as we anticipate making updates to the model list.

Note that we list research relevance based on studies related to SARS (SARS-CoV). There is little to no current information on specific relevance of particular animal models to COVID-19 (SARS-CoV-2).

COVID-19 Disease Models

Ace2 Knockout Mouse

Model #Model NameRelevance to COVID-19
TF3738Ace2 Knockout MouseAcute 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.1,2, 3
The Ace2 Knockout Mouse was generated by Lexicon Pharmaceuticals and is part of Taconic's Knockout Repository under model # TF3738. Lexicon has generously agreed to support distribution of this model under subsidized pricing and simple terms. Taconic is recovering 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, if you have interest please let us know.

Please register your interest in using this model for COVID-19 research.

Tmprss2 Knockout Mouse

Model #Model NameRelevance to COVID-19
TF3746Tmprss2 Knockout MouseTMPRSS2 is involved in SARS-CoV-2 entry into cells. Inhibition of this protein may constitute a treatment/prophylaxis mechanism. Tmprss22 knockout mice may be useful in studying COVID-19 disease pathogenesis.1,4
This model is currently cryopreserved. Taconic is currently assessing demand and will consider subsidized distribution based on demand and model utility for COVID-19 research. Please contact us if you are interested in using this model for COVID-19 research.

Stat1 Knockout Mouse

Model #Model NameRelevance to COVID-19
2045Stat1Stat1 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.5,6,7,8

Inbred Mice

Model #Model NameRelevance to COVID-19
BALB

BALJBO
BALB/c

BALB/c Bom
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.8

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 seen in COVID-19.9 Taconic is holding BALB/c retired female breeders in large quantities to facilitate studies using aged mice. As of March 20, 2020, inventory is at ~7 mo of age and will be held held to 11-12 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. When mouse-adapted SARS-CoV2 isolates become available, inbred mice may be useful for studies of vaccines, antiviral drugs and disease pathogenesis.10
B6

B6JBOM
Black 6

B6JBom
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.8

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. 11
129S6129SVEYoung 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.8

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. 11
SFB: Segmented Filamentous Bacteria may elevate the expression of coronavirus receptors in the murine small intestine.12 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.

Antibody Development and Production

Model #Model NameRelevance to COVID-19
BALB

BALJBO

SW

ICRSC
BALB/c

BALB/c Bom

Swiss Webster

ICR scid
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 mice (for mouse hybridomas) or ICR scid mice (for mouse or xenogeneic hybridomas) for in vivo production.

Taconic BALB have been used to generate SARS-CoV-neutralizing antibodies. 13

Vaccine Research and Development

Transgenic HLA Mice

Model #Model NameRelevance to COVID-19
9659

9660

9661

9662

9663

9664

4149
HLA-A2.1

HLA-A11

HLA-B7

HLA-A1

HLA-A24

HLA-B44

Abb Knockout/Transgenic HLA-DR4
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.

Humanized Immune System Mice

Model #Model NameRelevance to COVID-19
huPBMC-NOG

huPBMC-14957

HSCCB-NOG

HSCCB-13395
huPBMC-NOG

huPBMC-B2m-NOG

huNOG

huNOG-EXL
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.14

Scientific Services

Colony Management Solutions

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.

Model Generation Solutions

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.

Note: "InThisTogether" discounts valid for orders that ship by Sept 30, 2020, with the exception of humanized immune system mice which must ship by June 30, 2020.
References:

1 Hoffmann, M.; Kleine-Weber, H.; Schroeder, S.; Krüger, N.; Herrler, T.; Erichsen, S.; Schiergens, T. S.; Herrler, G.; Wu, N.-H.; Nitsche, A.; Müller, M. A.; Drosten, C.; Pöhlmann, S. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell 2020.

2 Imai, Y.; Kuba, K.; Rao, S.; Huan, Y.; Guo, F.; Guan, B.; Yang, P.; Sarao, R.; Wada, T.; Leong-Poi, H.; Crackower, M. A.; Fukamizu, A.; Hui, C.-C.; Hein, L.; Uhlig, S.; Slutsky, A. S.; Jiang, C.; Penninger, J. M. Angiotensin-Converting Enzyme 2 Protects from Severe Acute Lung Failure. Nature 2005, 436 (7047), 112-116.

3 Kuba, K.; Imai, Y.; Rao, S.; Gao, H.; Guo, F.; Guan, B.; Huan, Y.; Yang, P.; Zhang, Y.; Deng, W.; Bao, L.; Zhang, B.; Liu, G.; Wang, Z.; Chappell, M.; Liu, Y.; Zheng, D.; Leibbrandt, A.; Wada, T.; Slutsky, A. S.; Liu, D.; Qin, C.; Jiang, C.; Penninger, J. M. A Crucial Role of Angiotensin Converting Enzyme 2 (ACE2) in SARS Coronavirus-Induced Lung Injury. Nature Medicine 2005, 11 (8), 875-879.

4 Iwata-Yoshikawa, N.; Okamura, T.; Shimizu, Y.; Hasegawa, H.; Takeda, M.; Nagata, N. TMPRSS2 Contributes to Virus Spread and Immunopathology in the Airways of Murine Models after Coronavirus Infection. Journal of Virology 2019, 93 (6).

5 Hogan, R. J.; Gao, G.; Rowe, T.; Bell, P.; Flieder, D.; Paragas, J.; Kobinger, G. P.; Wivel, N. A.; Crystal, R. G.; Boyer, J.; Feldmann, H.; Voss, T. G.; Wilson, J. M. Resolution of Primary Severe Acute Respiratory Syndrome-Associated Coronavirus Infection Requires Stat1. Journal of Virology 2004, 78 (20), 11416-11421.

6 Frieman, M. B.; Chen, J.; Morrison, T. E.; Whitmore, A.; Funkhouser, W.; Ward, J. M.; Lamirande, E. W.; Roberts, A.; Heise, M.; Subbarao, K.; Baric, R. S. SARS-CoV Pathogenesis Is Regulated by a STAT1 Dependent but a Type I, II and III Interferon Receptor Independent Mechanism. PLoS Pathogens 2010, 6 (4).

7 Graham, R. L.; Becker, M. M.; Eckerle, L. D.; Bolles, M.; Denison, M. R.; Baric, R. S. A Live, Impaired-Fidelity Coronavirus Vaccine Protects in an Aged, Immunocompromised Mouse Model of Lethal Disease. Nature Medicine 2012, 18 (12), 1820-1826.

8 Subbarao, K.; Roberts, A. Is There an Ideal Animal Model for SARS? Trends in Microbiology 2006, 14 (7), 299-303.

9 Roberts, A.; Paddock, C.; Vogel, L.; Butler, E.; Zaki, S.; Subbarao, K. Aged BALB/c Mice as a Model for Increased Severity of Severe Acute Respiratory Syndrome in Elderly Humans. Journal of Virology 2005, 79 (9), 5833-5838.

10 Day, C. W.; Baric, R.; Cai, S. X.; Frieman, M.; Kumaki, Y.; Morrey, J. D.; Smee, D. F.; Barnard, D. L. A New Mouse-Adapted Strain of SARS-CoV as a Lethal Model for Evaluating Antiviral Agents in Vitro and in Vivo. Virology 2009, 395 (2), 210-222.

11 Roberts, A.; Lamirande, E. W.; Vogel, L.; Jackson, J. P.; Paddock, C. D.; Guarner, J.; Zaki, S. R.; Sheahan, T.; Baric, R.; Subbarao, K. Animal Models and Vaccines for SARS-CoV Infection. Virus Research 2008, 133 (1), 20-32v.

12 Feng, Z.; Wang, Y.; Qi, W. The Small Intestine, an Underestimated Site of SARS-CoV-2 Infection: From Red Queen Effect to Probiotics. 2020.

13 Faber, M.; Lamirande, E. W.; Roberts, A.; Rice, A. B.; Koprowski, H.; Dietzschold, B.; Schnell, M. J. A Single Immunization with a Rhabdovirus-Based Vector Expressing Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) S Protein Results in the Production of High Levels of SARS-CoV-Neutralizing Antibodies. Journal of General Virology 2005, 86 (5), 1435-1440.

14 Okada, M.; Okuno, Y.; Hashimoto, S.; Kita, Y.; Kanamaru, N.; Nishida, Y.; Tsunai, Y.; Inoue, R.; Nakatani, H.; Fukamizu, R.; Namie, Y.; Yamada, J.; Takao, K.; Asai, R.; Asaki, R.; Kase, T.; Takemoto, Y.; Yoshida, S.; Peiris, J.; Chen, P.-J.; Yamamoto, N.; Nomura, T.; Ishida, I.; Morikawa, S.; Tashiro, M.; Sakatani, M. Development of Vaccines and Passive Immunotherapy against SARS Corona Virus Using SCID-PBL/Hu Mouse Models. Vaccine 2007, 25 (16), 3038-3040.