Frontiers in Physiology (Oct 2022)

A novel murine model of atrial fibrillation by diphtheria toxin-induced injury

  • Theresa Trieu,
  • Philbert Mach,
  • Kaitlyn Bunn,
  • Vincent Huang,
  • Jamie Huang,
  • Christine Chow,
  • Haruko Nakano,
  • Viviana M. Fajardo,
  • Marlin Touma,
  • Shuxun Ren,
  • Yibin Wang,
  • Yibin Wang,
  • Atsushi Nakano,
  • Atsushi Nakano,
  • Atsushi Nakano

DOI
https://doi.org/10.3389/fphys.2022.977735
Journal volume & issue
Vol. 13

Abstract

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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.

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