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Figure 1. Patient-related LMNA mutant mouse models. Most animal models are generated based on Lmna mutation or deletion in cardiomyocytes and have contributed to investigations on DCM pathogenesis. The current fibroblast-specific Lmna-deficient mice demonstrated a similar DCM phenotype compared to cardiomyocyte Lmna-deficient models, with the signature of growth retardation, arrhythmia, and myocardial fibrosis, and senescence-associated secretory phenotype. Mechanistic studies showed upregulation of TGFβ signaling, activation of DNA damage response and apoptosis, and cell senescence. Collectively, cardiac fibroblasts with Lmna deficiency jointly contribute to DCM with cardiomyocytes. With this discovery, the non-cardiomyocytes are emerging as important new players in the pathogenesis of LMNA-DCM. (Created with BioRender.com).