Phenotypes associated with this allele

• Allele Symbol: Col1a1^{tm1(KRT18-ACE2)Irb}
• Allele Name: targeted mutation 1, Institut de Recerca Biomedica
• Allele ID: MGI:8219533
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Col1a1^tm1(KRT18-ACE2)Irb/Col1a1^+	involves: 129S4/SvJae * C57BL/6	MGI:8219613

Genotype
MGI:8219613

ht1

• Allelic Composition: Col1a1^{tm1(KRT18-ACE2)Irb}/Col1a1⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6

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

homeostasis/metabolism

increased cytokine level ( J:368665 )

• SARS-CoV-2 B.1 infected mice show an increase in cytokine and chemokine levels, with peak IP-10 and IL-6 levels at 3 dpi which decrease by 14 dpi and peak IFN-gamma, MCP-1 and MIP1Beta levels at 7 dpi which decay afterwards

• levels of inflammatory mediators at 7 dpi with SARS-CoV-2 B.1 are comparable to Tg(K18-ACE2)2Prlmn mice at the time of euthanasia (6-7 dpi)

immune system

increased cytokine level ( J:368665 )

• SARS-CoV-2 B.1 infected mice show an increase in cytokine and chemokine levels, with peak IP-10 and IL-6 levels at 3 dpi which decrease by 14 dpi and peak IFN-gamma, MCP-1 and MIP1Beta levels at 7 dpi which decay afterwards

• levels of inflammatory mediators at 7 dpi with SARS-CoV-2 B.1 are comparable to Tg(K18-ACE2)2Prlmn mice at the time of euthanasia (6-7 dpi)

interstitial pneumonia ( J:368665 )

• SARS-CoV-2 B.1 infected mice show development of bronchointerstitial pneumonia characterized by multifocal increased thickness of interalveolar wall, presence of macrophage-like cells into alveoli surrounding bronchi and bronchiole, and hyperplasia of type II pneumocytes; lesions evolve from mild and multifocal by 3 dpi to moderate by 14 dpi, with increasing lymphoplasmacytic infiltration until the end of study

• mice reaching the humane endpoint display areas of severe bronchointerstitial pneumonia

increased susceptibility to Coronaviridae infection ( J:368665 )

• mice challenged intranasally with SARS-CoV-2 B.1 D614G isolate exhibit weight loss and show mild clinical signs with no neurological signs indicating less pathogenic infection than in Tg(K18-ACE2)2Prlmn mice

• only 3 mice challenged intranasally with SARS-CoV-2 B.1 D614G isolate required euthanasia by 6-10 dpi due to weight loss exceeding the 20% limit and convalescent mice start to regain weight after 9 dpi, reaching 90% of initial weight by 14 dpi

• mice challenged intranasally with SARS-CoV-2 B.1 isolate show widespread infection in the respiratory tract, with viral RNA levels peaking at 3 dpi and tending to decay over time up to 14 dpi and have high titers of neutralizing antibodies; mice that had to be euthanized still show high viral RNA loads but infectious viruses could not be recovered, suggesting that this is residual genetic material in dying cells

• SARS-CoV-2 nucleoprotein antigen detection decreases with time, showing clearance by 14 dpi and mice reaching the humane endpoint at 8-10 dpi show mild to moderate SARS-CoV-2 antigen mainly in bronchiolar epithelium

• low levels of viral loads are detected in the heart and salivary glands but not in muscle, intestine, liver, kidney, pancreas, lymph nodes or spleen and only 3 mice show low viral loads in the brain and mice that are euthanized lack detectable viral load in the brain

• however, no infective virus is detected by viral titration in the brain at any timepoint, no brain lesions are seen, and no SARS-CoV-2 NP antigen is detected in the brain

respiratory system

interstitial pneumonia ( J:368665 )

• SARS-CoV-2 B.1 infected mice show development of bronchointerstitial pneumonia characterized by multifocal increased thickness of interalveolar wall, presence of macrophage-like cells into alveoli surrounding bronchi and bronchiole, and hyperplasia of type II pneumocytes; lesions evolve from mild and multifocal by 3 dpi to moderate by 14 dpi, with increasing lymphoplasmacytic infiltration until the end of study

• mice reaching the humane endpoint display areas of severe bronchointerstitial pneumonia

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
long COVID		DOID:0080848		J:368665
severe acute respiratory syndrome		DOID:2945		J:368665