Phenotypes Associated with This Genotype

Genotype
MGI:6402832

• Allelic Composition: Tg(CAG-ACE2)AC70Ctkt/0
• Genetic Background: either: (involves: BALB/c * C3H/HeJ * C57BL/6J) or (involves: C3H/HeJ * C57BL/6 * C57BL/6J)

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

mortality/aging

increased susceptibility to Coronaviridae infection induced morbidity/mortality ( J:117824 )

• mice infected with the Urbani strain of the severe acute respiratory syndrome coronavirus (SARS-CoV) die within 4-8 days post infection (dpi) unlike infected wild-type controls

immune system

abnormal cytokine level ( J:117824 )

• SARS-CoV-infected mice develop a strong inflammatory cytokine reaction that occurs later and more intensely in the brain than in the lungs

• SARS-CoV-infected mice show elevated levels of IL-1beta, IL-12p40, IL-12p70, CXCL1, RANTES, and MCP-1 in the lungs, elevated levels of IL-6, IL-12p40, G-CSF, CXCL1, MIP-1alpha, and MCP-1 in the brains and increased secretion of IL-1alpha, IL-1beta, GM-CSF, IL-12p70 and RANTES in the brain

interstitial pneumonia ( J:117824 )

• SARS-CoV-infected mice exhibit interstitial pneumonia, with diffuse alveolar damage, extensive alveolar collapse, and filling of remaining alveoli with fluid and desquamated epithelial cells, inflammatory infiltrate in the pulmonary interstitium

increased susceptibility to Coronaviridae infection ( J:117824 )

• mice show increased susceptibility to intranasal infection with the Urbani strain of the severe acute respiratory syndrome coronavirus (SARS-CoV) , developing an acute wasting syndrome including ruffled fur, lethargy, and rapid, shallow breathing, accompanied by persistent weight loss that reaches up to 35-40% in some mice, and a period of immobility lasting 1-3 days before death, showing higher viral titers, and dying within 4-8 days post infection (dpi) compared to wild-type controls

• mice infected with SARS-CoV through the intraperitoneal route show signs of illness at 4 dpi and exhibit high viral titers in the brain but not in the lungs

• maximum viral titers are seen in the lungs within 1-2 dpi and then gradually decrease while low viral titers are seen in the brain on 2 dpi and increase at 3 dpi and remain high until death

• high levels of SARS-CoV antigen are detected in bronchial epithelial cells, in vascular smooth muscle and ganglion cells in the lungs, in neurons and glial cells of the central nervous system and viral antigen is detected in the gastrointestinal tracts at 6 dpi, restricted to the subserosal ganglia and smooth muscle of the intestinal wall

• however, no necrosis or inflammatory reaction is seen in the CNS of SARS-CoV-infected mice

increased susceptibility to Coronaviridae infection induced morbidity/mortality ( J:117824 )

• mice infected with the Urbani strain of the severe acute respiratory syndrome coronavirus (SARS-CoV) die within 4-8 days post infection (dpi) unlike infected wild-type controls

respiratory system

interstitial pneumonia ( J:117824 )

• SARS-CoV-infected mice exhibit interstitial pneumonia, with diffuse alveolar damage, extensive alveolar collapse, and filling of remaining alveoli with fluid and desquamated epithelial cells, inflammatory infiltrate in the pulmonary interstitium

abnormal bronchus epithelium morphology ( J:117824 )

• SARS-CoV infected bronchial epithelial cells show cytoplasmic swelling and blebbing and are surrounded by moderate inflammatory mononuclear infiltrates

respiratory distress ( J:117824 )

• SARS-CoV-infected mice exhibit shallow breathing

cardiovascular system

vascular inflammation ( J:117824 )

• SARS-CoV-infected mice show mild to moderate vasculitis associated with presence of SARS-CoV antigen in the smooth muscle of blood vessels

homeostasis/metabolism

abnormal cytokine level ( J:117824 )

• SARS-CoV-infected mice develop a strong inflammatory cytokine reaction that occurs later and more intensely in the brain than in the lungs

• SARS-CoV-infected mice show elevated levels of IL-1beta, IL-12p40, IL-12p70, CXCL1, RANTES, and MCP-1 in the lungs, elevated levels of IL-6, IL-12p40, G-CSF, CXCL1, MIP-1alpha, and MCP-1 in the brains and increased secretion of IL-1alpha, IL-1beta, GM-CSF, IL-12p70 and RANTES in the brain

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
severe acute respiratory syndrome		DOID:2945		J:117824