Phenotypes Associated with This Genotype

Genotype
MGI:6415340

• Allelic Composition: Tg(FOXJ1-ACE2)1Rba/0
• Genetic Background: involves: C3H * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

immune system

decreased lymphocyte cell number ( J:288386 )

• SARS-CoV-2 infected mice that die show decreased lymphocyte numbers

interstitial pneumonia ( J:288386 )

• SARS-CoV-2-infected mice show different levels of pneumonia throughout the infection course

• at 1 dpi, mice show minor multifocal lesions in the lung, some thickening of alveolar walls with monocyte and lymphocyte infiltration and an increase in macrophages and lymphocytes in some alveolar spaces with minor exudation of fibrin

• at 3 dpi, moderate interstitial pneumonia is seen, with multifocal lesions, increased inflammatory cells at peri-bronchial and peri-vascular infiltration, and fibroblast hyperplasia with exudation of fibrin and protein edema in some alveoli

• after 5 dpi, 72.7% of mice show mild peri-bronchial and peri-vascular infiltration and 27.3% of mice show more severe pneumonia, with peri-bronchial and peri-vascular mixed inflammatory cell infiltration, fibroplasia, congestion, edema with hyaline membrane formation with some blocked terminal bronchioles and necrosis in some alveolar cells

increased susceptibility to Coronaviridae infection ( J:288386 , J:287092 )

• deceased mice show viral antigens in the brain (J:288386)

• viral antigens are seen in the bronchial epithelial cells and alveolar cells of the lungs (J:288386)

• a subset of mice infected intranasally with SARS-CoV-2 show decreased body weight from days 4 to 6 post-infection, show noticeable respiratory distress and neurological symptoms (J:288386)

• however, a subset of SARS-CoV-2 infected mice survive to the endpoint of the study without symptoms (J:288386)

• viral RNA is detected in all lungs from 1 dpi with SARS-CoV-2 and increases slowly until 5 dpi and then decreases beginning 7 dpi; low levels of viral RNA is seen in the eyes and hearts of some of the mice (J:288386)

• levels of neutrophils and monocytes begin to increase in the peripheral blood at day 1 of SARS-CoV-2 infection, peak at day 3, and decrease at 5-7 days post-infection (dpi) (J:288386)

• 10-20 week old mice infected with the bat SARS-like coronavirus WIV1 (WIV1-CoV), show increased susceptibility to infection compared to wild-type mice but less than when infected with SARS-CoV Urbani (J:287092)

• mice infected with WIV1-CoV, show minimal weight loss until late times when mice either lose less than or more than 10% of their body weight (J:287092)

• mice infected with WIV1-CoV show 100-fold higher titers than in wild-type mice (J:287092)

• all mice infected with SARS-CoV Urbani lose more than 20% body weight and maintain replication in the lung and brain following infection (J:287092)

• mice with more than 10% weight loss following WIV1-CoV infection produce robust viral replication in the brain, but lower titers in the lungs (J:287092)

• mice that maintain minimal weight less of less than 10% following WIV1-CoV infection show minimal titers in both the lung and brain after 7 days, indicating a sufficient adaptive immune response (J:287092)

• mice treated with antibody 227.14 one day before infection with either SARS-CoV or WIV1-CoV show no detectable virus in lungs (J:287092)

increased susceptibility to Coronaviridae infection induced morbidity/mortality ( J:288386 , J:287092 )

• mice infected with SARS-CoV-2 show 50% lethality (J:288386)

• 10-20 week old mice infected with SARS-CoV Urbani show rapid weight loss and death between days 4 and 5 of infection (J:287092)

• 10-20 week old mice infected with the bat SARS-like coronavirus WIV1 show an approximate 50% lethality by 7 days post infection (J:287092)

• mice treated with a monoclonal antibody derived from B cells from SARS-CoV-infected patients, antibody 227.14, one day before infection show protection from lethal SARS-CoV Urbani or WIV-CoV challenge (J:287092)

cardiovascular system

pulmonary vascular congestion ( J:288386 )

• SARS-CoV-2-infected mice that develop severe pneumonia show pulmonary congestion

abnormal myocardial fiber morphology ( J:288386 )

• SARS-CoV-2-infected mice show edema in some cardiomyocytes

• SARS-CoV-2-infected mice show several necrotic myocytes in heart tissue

mortality/aging

increased susceptibility to Coronaviridae infection induced morbidity/mortality ( J:288386 , J:287092 )

• mice infected with SARS-CoV-2 show 50% lethality (J:288386)

• 10-20 week old mice infected with SARS-CoV Urbani show rapid weight loss and death between days 4 and 5 of infection (J:287092)

• 10-20 week old mice infected with the bat SARS-like coronavirus WIV1 show an approximate 50% lethality by 7 days post infection (J:287092)

• mice treated with a monoclonal antibody derived from B cells from SARS-CoV-infected patients, antibody 227.14, one day before infection show protection from lethal SARS-CoV Urbani or WIV-CoV challenge (J:287092)

hematopoietic system

decreased lymphocyte cell number ( J:288386 )

• SARS-CoV-2 infected mice that die show decreased lymphocyte numbers

homeostasis/metabolism

increased circulating aspartate transaminase level ( J:288386 )

• SARS-CoV-2-infected mice that die show increased aspartate transaminase levels

abnormal lung thrombosis ( J:288386 )

• hyaline thrombus and fibrin are seen in severely SARS-CoV-2-infected lungs

increased creatine kinase level ( J:288386 )

• SARS-CoV-2-infected mice show higher levels of creatine kinase than control mice

pulmonary edema ( J:288386 )

• SARS-CoV2-infected mice that develop severe pneumonia exhibit edema

muscle

abnormal myocardial fiber morphology ( J:288386 )

• SARS-CoV-2-infected mice show edema in some cardiomyocytes

• SARS-CoV-2-infected mice show several necrotic myocytes in heart tissue

respiratory system

pulmonary vascular congestion ( J:288386 )

• SARS-CoV-2-infected mice that develop severe pneumonia show pulmonary congestion

pulmonary edema ( J:288386 )

• SARS-CoV2-infected mice that develop severe pneumonia exhibit edema

interstitial pneumonia ( J:288386 )

• SARS-CoV-2-infected mice show different levels of pneumonia throughout the infection course

• at 1 dpi, mice show minor multifocal lesions in the lung, some thickening of alveolar walls with monocyte and lymphocyte infiltration and an increase in macrophages and lymphocytes in some alveolar spaces with minor exudation of fibrin

• at 3 dpi, moderate interstitial pneumonia is seen, with multifocal lesions, increased inflammatory cells at peri-bronchial and peri-vascular infiltration, and fibroblast hyperplasia with exudation of fibrin and protein edema in some alveoli

• after 5 dpi, 72.7% of mice show mild peri-bronchial and peri-vascular infiltration and 27.3% of mice show more severe pneumonia, with peri-bronchial and peri-vascular mixed inflammatory cell infiltration, fibroplasia, congestion, edema with hyaline membrane formation with some blocked terminal bronchioles and necrosis in some alveolar cells

pulmonary necrosis ( J:288386 )

• SARS-CoV-2-infected mice that develop severe pneumonia show necrosis in some alveolar cells

respiratory distress ( J:288386 )

• a subset of mice infected with SARS-CoV-2 show respiratory distress

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Coronavirus infectious disease		DOID:0080599		J:287092
COVID-19		DOID:0080600		J:288386
severe acute respiratory syndrome		DOID:2945		J:287092