title: Mice transgenic for human angiotensin-converting enzyme 2 provide a model for SARS coronavirus infection.
abstract: To establish a small animal model of severe acute respiratory syndrome (SARS), we developed a mouse model of human severe acute respiratory syndrome coronavirus (SARS-CoV) infection by introducing the human gene for angiotensin-converting enzyme 2 (hACE2) (the cellular receptor of SARS-CoV), driven by the mouse ACE2 promoter, into the mouse genome. The hACE2 gene was expressed in lung, heart, kidney, and intestine. We also evaluated the responses of wild-type and transgenic mice to SARS-CoV inoculation. At days 3 and 7 postinoculation, SARS-CoV replicated more efficiently in the lungs of transgenic mice than in those of wild-type mice. In addition, transgenic mice had more severe pulmonary lesions, including interstitial hyperemia and hemorrhage, monocytic and lymphocytic infiltration, protein exudation, and alveolar epithelial cell proliferation and desquamation. Other pathologic changes, including vasculitis, degeneration, and necrosis, were found in the extrapulmonary organs of transgenic mice, and viral antigen was found in brain. Therefore, transgenic mice were more susceptible to SARS-CoV than were wild-type mice, and susceptibility was associated with severe pathologic changes that resembled human SARS infection. These mice will be valuable for testing potential vaccine and antiviral drug therapies and for furthering our understanding of SARS pathogenesis.
authors.affiliation: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, PR China.
authors.forename: Xiu-Hong
authors.initials: XH
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.forename: Zan
authors.initials: Z
authors.lastname: Tong
authors.forename: Yan-Xia
authors.initials: YX
authors.lastname: Liu
authors.forename: Lian-Feng
authors.initials: LF
authors.lastname: Zhang
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.forename: Hong
authors.initials: H
authors.lastname: Gao
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Liu
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Ma
authors.forename: Yan-Feng
authors.initials: YF
authors.lastname: Xu
authors.forename: Ming-Xiao
authors.initials: MX
authors.lastname: Ding
authors.forename: Hong-Kui
authors.initials: HK
authors.lastname: Deng
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005818:Genetic Engineering; D020022:Genetic Predisposition to Disease; D006801:Humans; D008168:Lung / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D045169:Severe Acute Respiratory Syndrome / Q000235:genetics / Q000473:pathology / Q000821:virology*
chemical_list: D012333:RNA, Messenger; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2