Comparative multi-omics analyses of cardiac mitochondrial stress in three mouse models of frataxin deficiency

Nicole M. Sayles, Jill S. Napierala, Josef Anrather, Nadège Diedhiou, Jixue Li, Marek Napierala, Hélène Puccio, Giovanni Manfredi; Comparative multi-omics analyses of cardiac mitochondrial stress in three mouse models of frataxin deficiency. Dis Model Mech 2023; dmm.050114. doi: doi:10.1242/dmm.050114

Transcriptional changes were found in all models, but differentially expressed genes consistent with cardiomyopathy and ISRmt were only identified in FxnG127V hearts. However, these changes were surprisingly mild even at an advanced age (18-months), despite a severe decrease in FXN levels to 1% of WT. These findings indicate that the mouse heart has low reliance on FXN, highlighting the difficulty in modeling genetically relevant FA cardiomyopathy.

Comparative multi-omics analyses of cardiac mitochondrial stress in three mouse models of frataxin deficiency