COVID-19 transgenic mouse model
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covid-19 HACE2 transgenic mouse model
IITRI has developed a robust model for COVID-19 using the K18 – humanized ACE2 transgenic mouse model (Jackson Labs).
Below is a basic study description and design, although IITRI can provide specialized study designs based on your needs. Contact us today to learn more and discuss how we can partner for SARS-CoV-2 animal studies.
| Species Information | K18 – hACE2 transgenic mice (Jax) |
| Study Duration | Sponsor dependent (7-14+ typical) |
| Challenge Dosage and Strains |
Intranasal (LD50-LD100); wildtype USA-WA1/2020), all relevant variants
|
| Drug administration | Aerosol, PO, IV, IN, SC (inquire about others) |
|
Possible Endpoints – General clinical observations – Body Weight – Tissue viral burden by TCID50 and/or RT-qPCR neutralizing antibody titer – Histopathology of tissues, to be evaluated with standard H.E. staining – Cytokine expression by RT-qPCR and/or ELISA
|
| Basic Study Design |
WA1: LD50=2-5E2 TCID50, recommended 5-10xLD50= 1-5E3to4 TCID50
Primary endpoints
– Mortality main endpoint. Starts on Day 5-6 and peaks on Day 8-9
– Bodyweight loss up to 20-25%. Starts on Day 4-5 peaks on Day 8-9
Secondary endpoints
– Viral load in lungs
– TCID50 (infectious virus). Starts on Day 1, peaks on Day 2-3
– RT-qPCR (prescence of genomic viral RNA). Starts on Day 1, peaks on Day 2-3
– RT-qPCR (active viral replication/transcription). Starts on Day 1, peaks on Day 2-3
– Viral load in upper respiratory tract
– TCID50 (infectious virus). Starts on Day 1, peaks on Day 2-3, very inconsistent in WA1-K18hACE2
– RT-qPCR (prescence of genomic viral RNA). Starts on Day 1, peaks on Day 2-3.
– RT-qPCR (active viral replication/transcription). Starts on Day 1, peaks on Day 2-3, very inconsistent in WA1-K18hACE2
– Viral load in swabs (virus shedding)
– TCID50 (infectious virus). Starts on Day 1, peaks on Day 2-3
– RT-qPCR (prescence of genomic viral RNA). Starts on Day 1, peaks on Day 2-3, lingers until Day 14
– Cytokines
– RT-qPCR (gene expression)
– Flow cytometry (Anti-Virus Response Panel multiplex bead-based assay)
– Histopathology of lungs. Day 2-3 (peak of disease) vs Day 14 (sequelae)
Delta B.1.617.2: LD50=<1-5E1 TCID50, recommended 10xID50= 1-5E2 TCID50
Lethal model in Mice.
Omicron BA.1 and BA.5 : Recommended 10XID50= 9E6 TCID50-in VAT or 3.76E5 TCID50-in Calu-3
– Not lethal model
– Bodyweight loss. Starts on Day 4-5, peak on Day 7 and then they recovered.
Primary endpoints
– Viral load in lungs
-TCID50 (infectious virus). Starts on Day 1, peaks on Day 2-3
– RT-qPCR (prescence of genomic viral RNA). Starts on Day 1, peaks on Day 2-3
– RT-qPCR (active viral replication/transcription).
– Viral load in upper respiratory tract
– TCID50 (infectious virus). Starts on Day 1, peaks on Day 2-3
– RT-qPCR (prescence of genomic viral RNA). Starts on Day 1, peaks on Day 2-3.
– Viral load in swabs (virus shedding)
– RT-qPCR (prescence of genomic viral RNA). Starts on Day 1, peaks on Day 2-3, and goes down quickly
– TCID50 (infectious virus).
Secondary endpoints
– Cytokines
– RT-qPCR (gene expression)
– Flow cytometry (Anti-Virus Response Panel multiplex bead-based assay)
Read more about the ACE2 transgenic mouse model below:
https://www.jax.org/news-and-insights/2020/february/introducing-mouse-model-for-corona-virus
https://www.nature.com/articles/s41586-020-2787-6