Pre-clinical mouse models for the study of Covid19 and testing of therapeutic strategies

The ultimate objective of this proposal is to develop a genetically modified mouse, susceptible to being infected by the SARS-CoVi-2 virus. We propose two models. The first consists of a knockin model in which the murine Ace2 gene is replaced by the coding sequence of its human counterpart. We know that Ace2 knockout mice develop phenotypes that may not be rescued by the expression of the human protein. Therefore, and in parallel, we propose the generation of a transgenic model, by means of a BAC that contains all the regulatory sequences for the expression of the murine Ace2 gene, and in which the coding sequence of said gene is replaced by that of the human gene ( cDNA). In both models, concomitant with the expression of the human ACE2 protein, the fluorescent protein tdTomatoo will be expressed, in order to be able to easily detect and isolate cells susceptible to being infected by the SARS-CoVi-2 virus.