Browsing by Subject "Pigs"

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    Animal Models for COVID-19: More to the Picture Than ACE2, Rodents, Ferrets, and Non-human Primates. A Case for Porcine Respiratory Coronavirus and the Obese Ossabaw Pig
    (Frontiers Media, 2020-09-25) Heegaard, Peter M. H.; Sturek, Michael; Alloosh, Mouhamad; Belsham, Graham J.; Anatomy and Cell Biology, School of Medicine
    The ongoing COVID-19 pandemic caused by infection with SARS-CoV-2 has created an urgent need for animal models to enable study of basic infection and disease mechanisms and for development of vaccines, therapeutics, and diagnostics. Most research on animal models for COVID-19 has been directed toward rodents, transgenic rodents, and non-human primates. The primary focus has been on the angiotensin-converting enzyme 2 (ACE2), which is a host cell receptor for SARS-CoV-2. Among investigated species, irrespective of ACE2 spike protein binding, only mild (or no) disease has occurred following infection with SARS-CoV-2, suggesting that ACE2 may be necessary for infection but is not sufficient to determine the outcome of infection. The common trait of all species investigated as COVID models is their healthy status prior to virus challenge. In contrast, the vast majority of severe COVID-19 cases occur in people with chronic comorbidities such as diabetes, obesity, and/or cardiovascular disease. Healthy pigs express ACE2 protein that binds the viral spike protein but they are not susceptible to infection with SARS-CoV-2. However, certain pig breeds, such as the Ossabaw pig, can reproducibly be made obese and show most aspects of the metabolic syndrome, thus resembling the more than 80% of the critically ill COVID-19 patients admitted to hospitals. We urge considering infection with porcine respiratory coronavirus of metabolic syndrome pigs, such as the obese Ossabaw pig, as a highly relevant animal model of severe COVID-19.
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    Reduced human platelet uptake by pig livers deficient in the asialoglycoprotein receptor 1 protein
    (Wiley, 2015-05) Paris, Leela L.; Estrada, Jose L.; Li, Ping; Blankenship, Ross L.; Sidner, Richard A.; Reyes, Luz M.; Montgomery, Jessica B.; Burlak, Christopher; Butler, James R.; Downey, Susan M.; Wang, Zheng-Yu; Tector, Matthew; Tector, A. Joseph; Surgery, School of Medicine
    BACKGROUND: The lethal thrombocytopenia that accompanies liver xenotransplantation is a barrier to clinical application. Human platelets are bound by the asialoglycoprotein receptor (ASGR) on pig sinusoidal endothelial cells and phagocytosed. Inactivation of the ASGR1 gene in donor pigs may prevent xenotransplantation-induced thrombocytopenia. METHODS: Transcription activator-like effector nucleases (TALENs) were targeted to the ASGR1 gene in pig liver-derived cells. ASGR1 deficient pig cells were used for somatic cell nuclear transfer (SCNT). ASGR1 knock out (ASGR1-/-) fetal fibroblasts were used to produce healthy ASGR1 knock out piglets. Human platelet uptake was measured in ASGR1+/+ and ASGR1-/- livers. RESULTS: Targeted disruption of the ASGR1 gene with TALENs eliminated expression of the receptor. ASGR1-/- livers phagocytosed fewer human platelets than domestic porcine livers during perfusion. CONCLUSIONS: The use of TALENs in liver-derived cells followed by SCNT enabled the production of healthy homozygous ASGR1 knock out pigs. Livers from ASGR1-/- pigs exhibit decreased human platelet uptake. Deletion of the ASGR1 gene is a viable strategy to diminish platelet destruction in pig-to-human xenotransplantation.