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10.1172/jci.insight.142032 http://scihub22266oqcxt.onion/10.1172/jci.insight.142032 32841215!7566707!32841215     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=32841215&cmd=llinks): Failed to open stream: HTTP request failed! 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Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease |pdf=|usr=}}{{32841215}} gab.com Text Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease JO: JCI Insight http://www.kidney.de/pget.php?&tw=1&pmid=32841215 #FOAvip The emergence of SARS-CoV-2 has created an international health crisis, and small animal models mirroring SARS-CoV-2 human disease are essential for medical countermeasure (MCM) development. Mice are refractory to SARS-CoV-2 infection owing to low-affinity binding to the murine angiotensin-converting enzyme 2 (ACE2) protein. Here, we evaluated the pathogenesis of SARS-CoV-2 in male and female mice expressing the human ACE2 gene under the control of the keratin 18 promoter (K18). In contrast to nontransgenic mice, intranasal exposure of K18-hACE2 animals to 2 different doses of SARS-CoV-2 resulted in acute disease, including weight loss, lung injury, brain infection, and lethality. Vasculitis was the most prominent finding in the lungs of infected mice. Transcriptomic analysis from lungs of infected animals showed increases in transcripts involved in lung injury and inflammatory cytokines. In the low-dose challenge groups, there was a survival advantage in the female mice, with 60% surviving infection, whereas all male mice succumbed to disease. Male mice that succumbed to disease had higher levels of inflammatory transcripts compared with female mice. To our knowledge, this is the first highly lethal murine infection model for SARS-CoV-2 and should be valuable for the study of SARS-CoV-2 pathogenesis and for the assessment of MCMs. Twit Text FOAVip Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease ????JCI Insight http://www.kidney.de/pget.php?&tw=1&pmid=32841215 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32841215 #FOAvip English Wikipedia <ref>{{Cite pmid|32841215}}</ref> Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease #MMPMID32841215 Golden JW; Cline CR; Zeng X; Garrison AR; Carey BD; Mucker EM; White LE; Shamblin JD; Brocato RL; Liu J; Babka AM; Rauch HB; Smith JM; Hollidge BS; Fitzpatrick C; Badger CV; Hooper JW JCI Insight 2020[Oct]; 5 (19): ä PMID32841215show ga The emergence of SARS-CoV-2 has created an international health crisis, and small animal models mirroring SARS-CoV-2 human disease are essential for medical countermeasure (MCM) development. Mice are refractory to SARS-CoV-2 infection owing to low-affinity binding to the murine angiotensin-converting enzyme 2 (ACE2) protein. Here, we evaluated the pathogenesis of SARS-CoV-2 in male and female mice expressing the human ACE2 gene under the control of the keratin 18 promoter (K18). In contrast to nontransgenic mice, intranasal exposure of K18-hACE2 animals to 2 different doses of SARS-CoV-2 resulted in acute disease, including weight loss, lung injury, brain infection, and lethality. Vasculitis was the most prominent finding in the lungs of infected mice. Transcriptomic analysis from lungs of infected animals showed increases in transcripts involved in lung injury and inflammatory cytokines. In the low-dose challenge groups, there was a survival advantage in the female mice, with 60% surviving infection, whereas all male mice succumbed to disease. Male mice that succumbed to disease had higher levels of inflammatory transcripts compared with female mice. To our knowledge, this is the first highly lethal murine infection model for SARS-CoV-2 and should be valuable for the study of SARS-CoV-2 pathogenesis and for the assessment of MCMs. |*Cause of Death[MESH] |*Disease Progression[MESH] |Angiotensin-Converting Enzyme 2[MESH] |Animals[MESH] |COVID-19[MESH] |Coronavirus Infections/*pathology/physiopathology[MESH] |Disease Models, Animal[MESH] |Female[MESH] |Humans[MESH] |Lung/pathology[MESH] |Male[MESH] |Mice[MESH] |Mice, Transgenic[MESH] |Pandemics[MESH] |Peptidyl-Dipeptidase A/*genetics[MESH] |Pneumonia, Viral/*pathology/physiopathology[MESH] |Severe Acute Respiratory Syndrome/*pathology/physiopathology[MESH] |Severity of Illness Index[MESH] |Survival Rate[MESH]Human angiotensin-converting enzyme 2 transgenic mice infected with SA(epmc).pdf DeepDyve Pubget Overpricing