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Mice transgenic for human angiotensin-converting enzyme 2 provide a model for SARS coronavirus infection.
Comp Med. 2007 Oct; 57(5):450-9.CM

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+Show Affiliations

Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, PR China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17974127

Citation

Yang, Xiu-Hong, et al. "Mice Transgenic for Human Angiotensin-converting Enzyme 2 Provide a Model for SARS Coronavirus Infection." Comparative Medicine, vol. 57, no. 5, 2007, pp. 450-9.
Yang XH, Deng W, Tong Z, et al. Mice transgenic for human angiotensin-converting enzyme 2 provide a model for SARS coronavirus infection. Comp Med. 2007;57(5):450-9.
Yang, X. H., Deng, W., Tong, Z., Liu, Y. X., Zhang, L. F., Zhu, H., Gao, H., Huang, L., Liu, Y. L., Ma, C. M., Xu, Y. F., Ding, M. X., Deng, H. K., & Qin, C. (2007). Mice transgenic for human angiotensin-converting enzyme 2 provide a model for SARS coronavirus infection. Comparative Medicine, 57(5), 450-9.
Yang XH, et al. Mice Transgenic for Human Angiotensin-converting Enzyme 2 Provide a Model for SARS Coronavirus Infection. Comp Med. 2007;57(5):450-9. PubMed PMID: 17974127.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mice transgenic for human angiotensin-converting enzyme 2 provide a model for SARS coronavirus infection. AU - Yang,Xiu-Hong, AU - Deng,Wei, AU - Tong,Zan, AU - Liu,Yan-Xia, AU - Zhang,Lian-Feng, AU - Zhu,Hua, AU - Gao,Hong, AU - Huang,Lan, AU - Liu,Ya-Li, AU - Ma,Chun-Mei, AU - Xu,Yan-Feng, AU - Ding,Ming-Xiao, AU - Deng,Hong-Kui, AU - Qin,Chuan, PY - 2007/11/3/pubmed PY - 2008/1/25/medline PY - 2007/11/3/entrez SP - 450 EP - 9 JF - Comparative medicine JO - Comp Med VL - 57 IS - 5 N2 - 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. SN - 1532-0820 UR - https://www.unboundmedicine.com/medline/citation/17974127/Mice_transgenic_for_human_angiotensin_converting_enzyme_2_provide_a_model_for_SARS_coronavirus_infection_ L2 - https://www.ingentaconnect.com/openurl?genre=article&issn=1532-0820&volume=57&issue=5&spage=450&aulast=Yang DB - PRIME DP - Unbound Medicine ER -