The primary goals of this Program Project application are to understand the function of pannexin channels in normal physiology, as well as well as under conditions of cardiovascular and inflammatory diseases. This Mouse Support Core/Core B will serve all projects in the following ways: (1) This core will provide the husbandry, genotyping and basic crossing of conditional Panx1 knockout mice to specific Cre strains; specifically, the Panx1fl/fl mice crossed to at least five different Cre strains that are relevant to studying cardiovascular and inflammatory diseases. (2) This Core will also help generate additional transgenic Panx1 mice for tissue-specific expression of Panx1-WT and variants. (3) The Core will generate Cre-mediated tissue-speficic knockouts of the Panx1-regulatory proteins Sik1 and LKB1. The key benefits of this Mouse Support Core are that it will help consolidate the breeding and mouse maintenance, save time and cost, and avoid variations due to colonies individually maintained by the four project leaders. As the previous funding period has shown, having a dedicated core to cross the various Cre strains will be a huge advantage to all four projects. Moreover, the innovative transgenic mouse models overexpressing wild type or mutant forms of Panx1 will help answer key questions posed in the four main Projects in additional unique ways. Collectively, these mouse strains/models and analyses tools generated are expected to be fundamentally important in advancing our work to human disease, and will also help the larger community of researchers studying pannexin channel function pertaining to many human diseases.
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