Fig. 5: Characterizing the ACE2 GEMM with SARS-CoV-2 infection.
From: Mouse genome rewriting and tailoring of three important disease loci
a,b, Lungs dissected from wild-type, K18-hACE2 (K18) and 116 kb-ACE2 (ACE2) mice infected with SARS-CoV-2 were analysed for nucleocapsid gene expression by RT–qPCR (a) and infectious viral levels by plaque assay (b). n = 4 independent mice for each group. SARS-CoV-2 levels were normalized to Actb and an uninfected control. F, female mice; M, male mice. c, Volcano plot of infected lungs versus uninfected lungs from 116 kb-ACE2 mice. Red, upregulated genes in infected lungs; blue, downregulated genes in infected lungs. Fold change cut-off is set to 2; adjusted P value (Wald test) cut-off is set to 0.01. d, Venn diagram of upregulated (cut-off is twofold) differentially expressed genes (DEGs) in wild-type (WT), K18-hACE2 and 116 kb-ACE2 lungs. e, RT–qPCR analysis of dACE2 in uninfected and SARS-CoV-2-infected lungs. n = 3 for uninfected lungs, n = 8 for infected lungs; 3 technical replicates were performed for each sample. Unpaired two-tailed, Mann–Whitney t-test. f, Histopathological analysis of lungs from female WT, K18-hACE2 and 116 kb-ACE2 mice by haematoxylin and eosin staining. Two lungs from independent infected mice were used; two spaced 5-μm sections from the same infected lung were stained and imaged. g,h, K18-hACE2 (n = 5) and 116 kb-ACE2 (n = 4) mice were intranasally infected with 105 PFU of SARS-CoV-2 and were monitored every other day for morbidity (g) and weight (h). Data are mean ± s.d. of biological replicates. i, Serological detection of anti-SARS-CoV-2 mouse IgG by ELISA. n = 4 independent mice for uninfected and infected groups. Box plots contain 25th to 75th percentiles of the data, the horizontal line in each box denotes the median value, and whiskers represent minima (low) and maxima (high).
