AUTHOR=Trieu Theresa , Mach Philbert , Bunn Kaitlyn , Huang Vincent , Huang Jamie , Chow Christine , Nakano Haruko , Fajardo Viviana M. , Touma Marlin , Ren Shuxun , Wang Yibin , Nakano Atsushi TITLE=A novel murine model of atrial fibrillation by diphtheria toxin-induced injury JOURNAL=Frontiers in Physiology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2022.977735 DOI=10.3389/fphys.2022.977735 ISSN=1664-042X ABSTRACT=

The treatment of atrial fibrillation (AF) continues to be a significant clinical challenge. While genome-wide association studies (GWAS) are beginning to identify AF susceptibility genes (Gudbjartsson et al., Nature, 2007, 448, 353–357; Choi et al., Circ. Res., 2020, 126, 200–209; van Ouwerkerk et al., Circ. Res., 2022, 127, 229–243), non-genetic risk factors including physical, chemical, and biological environments remain the major contributors to the development of AF. However, little is known regarding how non-genetic risk factors promote the pathogenesis of AF (Weiss et al., Heart Rhythm, 2016, 13, 1868–1877; Chakraborty et al., Heart Rhythm, 2020, 17, 1,398–1,404; Nattel et al., Circ. Res., 2020, 127, 51–72). This is, in part, due to the lack of a robust and reliable animal model induced by non-genetic factors. The currently available models using rapid pacing protocols fail to generate a stable AF phenotype in rodent models, often requiring additional genetic modifications that introduce potential sources of bias (Schüttler et al., Circ. Res., 2020, 127, 91–110). Here, we report a novel murine model of AF using an inducible and tissue-specific activation of diphtheria toxin (DT)-mediated cellular injury system. By the tissue-specific and inducible expression of human HB-EGF in atrial myocytes, we developed a reliable, robust and scalable murine model of AF that is triggered by a non-genetic inducer without the need for AF susceptibility gene mutations.