Table 6.

Models based on mouse-adapted strain of SARS-CoV-2

Animal models	Strains & Inoculation	Adaptive mutations	Outcomes				References
			Clinical signs	Pathogenesis	Infected organs	Virus shedding
(1) Wild-type BALB/c, nine-month-old	Original strain was IME-BJ05 passaged for 6 times in old BALB/c mice; Mouse adaption strain was named MASCp6; Inoculation dosage was 1.6 × 104 PFU with I.N. routes	5 nucleotide mutations distributed within ORF1ab, S and N gene; the key mutation in A23063T resulting in N501Y substitution in RBD of S protein	No significant weight changes or death	Mild to moderate pneumonia, interstitial pneumonia, vessel injured, with adherent inflammatory cells; self-recovered on 5 dpi	The most wildly infected organs: Lung, trachea, feces, intestine, heart, liver, spleen and brain on 3 dpi	Virus shedding was detected on 3, 5, 7 dpi; maximal virus titer 1010 copies/g in lung on 3 dpi	Gu et al.260
(2) Wild-type BALB/c, six-week-old	Original strain was IME-BJ05 passaged for 6 times in old BALB/c mice; Mouse adaption strain was named MASCp6; Inoculation dosage was 1.6 × 104 PFU with I.N. routes	5 nucleotide mutations distributed within ORF1ab, S and N gene; the key mutation in A23063T resulting in N501Y substitution in RBD of S protein	No significant weight changes or death	mild to moderate pneumonia, but much milder than the old mice	The most wildly infected organs were lung, trachea, feces, intestine, heart, liver and kidney observed on 5 dpi	Virus shedding was detected on 3, 5, 7 dpi; maximal virus titer 1011 copies/g in lung on 3 dpi, almost 10 folds higher than older BALB/c mice	Gu et al.260
(3) Wild-type BALB/c, 12-week-old	Original strain was SARS-CoV-2; Mouse adaption strain was named SARS-CoV-2 MA; Inoculation dosage was 1.0 × 105 PFU with I.N. routes	By revers genetics technology to make the mouse adaption strain, in which including RBD Q498T and P499Y substitutions	No weight loss or other clinical signs; loss of pulmonary function	No pathologic changes were described	Mainly infected lung, small nasal virus in nasal turbinate	Virus detected on 2, 4 dpi; maximal PFU appeared on 2 dpi, but almost cleared on 4 dpi	Dinnon et al.261
(4) Wild-type BALB/c, one-year-old	Original strain was SARS-CoV-2; Mouse adaption strain was named SARS-CoV-2 MA; Inoculation dosage was 1.0 × 105 PFU with I.N. routes	By revers genetics technology to make the mouse adaption strain, in which including RBD Q498T and P499Y substitutions	Weight loss near to 10% on 3 dpi, then recovered; presenting more severe loss of pulmonary function than young BALB/c mice	No. pathologic changes was described	Mainly infected lung, small nasal virus in nasal turbinate	Virus detected on 2, 4 dpi; The maximal PFU over 106 appeared on 2 dpi, but many mice almost cleared on 4 dpi	Dinnon et al.261