¹TUBITAK Marmara Research Center, TR-41470, Kocaeli - TÜRKİYE DOI : 10.9775/kvfd.2023.30229 The K18-hACE2 transgenic mice, a model animal having human ACE receptors, is employed in studies against the SARS-CoV-2 virus all over the world. Aged Balb/C mice utilized during the SARS-CoV outbreak were compared to non-T-cell, immunosuppressive Nude mice often employed in cancer research and K18-hACE2 transgenic mice used as a model animal against the SARS-CoV-2 virus challenge assay. At the same time, the role of the model animal K18-hACE2 transgenic mice in organs other than the lung was studied. The BSL3 facility was used for the challenge experiment in this study. In three groups, 105 TCID50 SARS-CoV-2 virus B.1.1.7 (the alpha variant was gavaged and intranasally administered to mice under anesthesia. The experiment was ended on the tenth day, and gross pathology was done. The viral load of SARSCoV- 2 was determined by RT-PCR after collecting the target organ lungs from all mice as well as the spleen, liver, heart, and kidneys from the K18-hACE2 transgenic mouse group. In comparison to Balb/C and Nude mice, the K18-hACE2 transgenic mouse model animal has been shown to be a suitable model against the SARS-CoV-2 virus in our study. At the same time, when the organs of K18-hACE2 transgenic mice were compared, viral load retention occurred in the target organ, the lung, with no significant retention in other organs. Keywords : COVID-19, In vivo challenge, Model animals, SARS-CoV-2