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

Sayles, N. M., Napierala, J. S., Anrather, J., Diedhiou, N., Li, J., Napierala, M., Puccio, H., & Manfredi, G. (2023). Comparative multi-omics analyses of cardiac mitochondrial stress in three mouse models of frataxin deficiency. bioRxiv; doi:10.1101/2023.02.03.526305 

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 extremely 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