Fig. 5. SARS-CoV-2-induced lung injury and ACE2 downregulation in hACE2 Tg mice.

a Western blot of human ACE2 protein in the lung lysates of uninfected hACE2 Tg mouse expressing human ACE2 under CAG promoter. b–c Virus titers (TCID₅₀) in the lysates of lung (b) and brain (c) prepared from hACE2 Tg mice intratracheally (i.t.) infected with SARS-CoV-2 (2 × 10³ TCID₅₀) at 2 dpi (n = 3), 4 dpi (n = 3), and 6 dpi (n = 4). dpi; days post infection. d Lung edema of wild-type and hACE2 Tg mice after SARS-CoV-2 infection. Wet/dry ratio of lung weight of wild type mice (n = 3 each for 0, 2, 4, and 7 dpi) and hACE2 Tg mice (n = 3 for 0 dpi, n = 5 each for 2 and 4 dpi, n = 6 for 7 dpi). e Lung injury score of wild-type and hACE2 Tg mice after SARS-CoV-2 infection. n = 7 for hACE2 Tg mice at 4 dpi, n = 6 for hACE2 Tg mice at 6 dpi, and n = 3 for other experimental groups. f–h Protein expression of human ACE2 and mouse Ace2 in the lungs of SARS-CoV-2-infected hACE2 Tg mice. Representative Western blots are shown (f). Human ACE2 (g) and mouse Ace2 (h) were normalized with Gapdh (n = 4 mice for 2 dpi, n = 6 each for 2 and 4 dpi). All values are means ± SEM. One-way ANOVA with Sidak’s multiple comparisons test (b–e, g, h). Numbers above square brackets show P values. Independent experiments were performed one time (b, c) or two times (a, d–h), and consistent results were obtained.