Phenotypes Associated with This Genotype

Genotype
MGI:6402641

• Allelic Composition: Tg(Ace2-ACE2)1Cqin/0
• Genetic Background: involves: ICR

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

immune system

lymph node hemorrhage ( J:141460 )

• some lymph nodes from SARS-CoV-infected mice severe hemorrhage

submandibular gland inflammation ( J:141460 )

• SARS-CoV-infected mice exhibit lymphocytic infiltrate in the submandibular gland

lymph node necrosis ( J:287631 )

• some lymph nodes from SARS-CoV-infected mice exhibit severe necrosis

pyelitis ( J:141460 )

• SARS-CoV-infected mice exhibit pyelitis

alveolitis ( J:141460 )

• SARS-CoV-infected mice exhibit desquamative pulmonary alveolitis and bronchitis and multinucleated macrophages in the alveoli

interstitial pneumonia ( J:141460 , J:287631 )

• SARS-CoV-infected mice exhibit more severe pulmonary damage accompanied by interstitial hyperemia, edema, inflammatory cell infiltration (both monocytes and lymphocytes), thickened interstitial, broken alveolar walls, extensive consolidation, compensatory emphysema and extensive hemorrhage (J:141460)

• lung tissues from SARS-CoV-2-infected mice show moderate interstitial pneumonia characterized by thickened alveolar septa with infiltration of inflammatory cells in 70-80% areas of lung tissues and accumulation of inflammatory cells in partial alveolar cavities at 3 dpi; pneumonia becomes mild at 7 dpi (J:287631)

• inflammatory cells in SARS-CoV2-infected mice include lymphocytes, macrophages, and neutrophils which accumulate in the alveolar interstitium and cause thickening of the alveolar walls (J:287631)

• lungs of SARS-CoV-2-infected mice show more macrophages, and T lymphocytes, with MAC2+ macrophages diffusely infiltrated in the alveolar cavities or focally aggregated in the thickened alveolar septum, CD3+ T lymphocytes dispersed or aggregated in the alveolar interstitium, and CD19+ B lymphocytes in the alveolar interstitium (J:287631)

increased susceptibility to Coronaviridae infection ( J:141460 , J:288244 , J:287631 )

• mice show increased susceptibility to infection with human acute respiratory syndrome coronavirus (SARS-CoV) strain PUMC01, showing greater viral titer in lungs than wild-type mice, slower clearing of virus, more severe pathologic changes and systemic toxic reaction (J:141460)

• SARS-CoV antigen is detected in vascular endothelial cells and epithelial cells of the alveoli and in cerebral neurocytes but no virus antigen is detected in the kidney, heart, liver, stomach or other organs (J:141460)

• 7 of 13 non-infected mice housed with SARS-CoV-2/WH-09/human/2020/CHN-infected mice develop antibody seropositivity indicating high risk of close contact transmission (J:288244)

• 3 of 10 naive mice exposed to respiratory droplets from SARS-CoV-2-infected mice via airflow transmission cages show seropositivity 14 days after exposure (J:288244)

• however, mice cannot be infected via aerosol inoculation until continued up to 25 minutes with high virus concentration (J:288244)

• mice show susceptibility to intranasal infection with the SARS-CoV-2 stock virus HB-01 (BetaCoV/Wuhan/IVDC-HB-01/2020|EPI_ISL_402119), with mice showing weight loss of up to 8% at 5 days post infection (dpi) that is not seen in wild-type controls and viral loads detected in lungs with highest virus titers detected at 3 dpi in the lungs (J:287631)

• specific IgG antibodies against S protein of SARS-CoV-2 are detected in the sera of infected mice at 21 dpi (J:287631)

• viral antigens are detected within alveolar macrophages, alveolar epithelia, and degenerative/desquamated bronchial epithelial cells of SARS-CoV-2-infected mice (J:287631)

• small amounts of viral antigens are detected in respiratory epithelial cells within non-lesional areas of the lungs (J:287631)

• infectious virus is isolated from the lungs at 1, 3, and 5 dpi, with highest viral titers at 3 dpi (J:287631)

• however, no lesions or viral antigens are seen in the myocardium, liver, spleen, kidney, cerebrum, intestine and testis of SARS-CoV-2-infected mice (J:287631)

growth/size/body

increased susceptibility to weight loss ( J:287631 )

• SARS-CoV-2-infected mice show weight loss, with up to 8% weight loss at 5 dpi

respiratory system

lung hemorrhage ( J:141460 )

• SARS-CoV-infected mice exhibit extensive hemorrhage in the lungs at 3 days post infection

pulmonary hyperemia ( J:141460 )

• SARS-CoV-infected mice exhibit interstitial hyperemia

alveolitis ( J:141460 )

• SARS-CoV-infected mice exhibit desquamative pulmonary alveolitis and bronchitis and multinucleated macrophages in the alveoli

interstitial pneumonia ( J:141460 , J:287631 )

• SARS-CoV-infected mice exhibit more severe pulmonary damage accompanied by interstitial hyperemia, edema, inflammatory cell infiltration (both monocytes and lymphocytes), thickened interstitial, broken alveolar walls, extensive consolidation, compensatory emphysema and extensive hemorrhage (J:141460)

• lung tissues from SARS-CoV-2-infected mice show moderate interstitial pneumonia characterized by thickened alveolar septa with infiltration of inflammatory cells in 70-80% areas of lung tissues and accumulation of inflammatory cells in partial alveolar cavities at 3 dpi; pneumonia becomes mild at 7 dpi (J:287631)

• inflammatory cells in SARS-CoV2-infected mice include lymphocytes, macrophages, and neutrophils which accumulate in the alveolar interstitium and cause thickening of the alveolar walls (J:287631)

• lungs of SARS-CoV-2-infected mice show more macrophages, and T lymphocytes, with MAC2+ macrophages diffusely infiltrated in the alveolar cavities or focally aggregated in the thickened alveolar septum, CD3+ T lymphocytes dispersed or aggregated in the alveolar interstitium, and CD19+ B lymphocytes in the alveolar interstitium (J:287631)

abnormal lung morphology ( J:287631 )

• SARS-CoV-2-infected mice develop gross lesions with focal to multifocal dark red discoloration in lung lobes at 3 dpi that progress to multifocal to coalescent scattered-dark reddish purple areas and focal nodules throughout the lungs at 5 dpi and damaged lungs become swollen and enlarged

pulmonary edema ( J:141460 )

• SARS-CoV-infected mice exhibit more severe pulmonary edema than infected wild-type mice

abnormal lung interstitium morphology ( J:287631 )

• SARS-CoV-2-infected mice show thickened alveolar interstitium wtih increased collagen fibers at 5 dpi

emphysema ( J:141460 )

• SARS-CoV-infected mice exhibit compensatory emphysema at 3 days post infection

abnormal bronchiole morphology ( J:287631 )

• detached bronchiolar epithelium is occasionally seen in affected bronchioles at 5 dpi with SARS-CoV-2

abnormal bronchiole epithelium morphology ( J:287631 )

• bronchiolar epithelial cells from SARS-CoV-2-infected mice show swelling and degeneration

cardiovascular system

abnormal glomerular capillary morphology ( J:141460 )

• SARS-CoV-infected mice exhibit dilated and engorged glomerular capillaries

blood vessel degeneration ( J:141460 )

• some blood vessels become degenerated in SARS-CoV-infected mice

abnormal heart morphology ( J:141460 )

• mild lymphocytic infiltration and sarcolemmal proliferation are present in cardiac interstitital tissue

lung hemorrhage ( J:141460 )

• SARS-CoV-infected mice exhibit extensive hemorrhage in the lungs at 3 days post infection

pulmonary hyperemia ( J:141460 )

• SARS-CoV-infected mice exhibit interstitial hyperemia

intracranial hemorrhage ( J:141460 )

• SARS-CoV-infected mice show brain hemorrhage

lymph node hemorrhage ( J:141460 )

• some lymph nodes from SARS-CoV-infected mice severe hemorrhage

vascular inflammation ( J:141460 )

• SARS-CoV-infected mice show brain vasculitis

digestive/alimentary system

abnormal intestinal mucosa morphology ( J:141460 )

• mucosal layers of the small intestine of SARS-CoV-infected mice show signs of edema, small vessel dilation, and lymphocyte infiltration

abnormal stomach mucosa morphology ( J:141460 )

• mucosal layers of the stomach of SARS-CoV-infected mice show signs of edema, small vessel dilation, and lymphocyte infiltration

submandibular gland inflammation ( J:141460 )

• SARS-CoV-infected mice exhibit lymphocytic infiltrate in the submandibular gland

homeostasis/metabolism

pulmonary edema ( J:141460 )

• SARS-CoV-infected mice exhibit more severe pulmonary edema than infected wild-type mice

liver/biliary system

hepatic necrosis ( J:141460 )

• SARS-CoV-infected mice exhibit patchy necrosis in the liver

nervous system

intracranial hemorrhage ( J:141460 )

• SARS-CoV-infected mice show brain hemorrhage

abnormal brain morphology ( J:141460 )

• SARS-CoV-infected mice exhibit brain damage including ependymitis, vasculitis, and hemorrhage

renal/urinary system

abnormal glomerular capillary morphology ( J:141460 )

• SARS-CoV-infected mice exhibit dilated and engorged glomerular capillaries

pyelitis ( J:141460 )

• SARS-CoV-infected mice exhibit pyelitis

abnormal renal tubule epithelium morphology ( J:141460 )

• SARS-CoV-infected mice show degeneration of proximal tubule epithelial cells

abnormal kidney interstitium morphology ( J:141460 )

• SARS-CoV-infected mice show lymphocytic infiltrate in the renal interstitia

endocrine/exocrine glands

submandibular gland inflammation ( J:141460 )

• SARS-CoV-infected mice exhibit lymphocytic infiltrate in the submandibular gland

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
COVID-19		DOID:0080600		J:287631 , J:288244
severe acute respiratory syndrome		DOID:2945		J:141460