Summary of project PR001794
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001794. The data can be accessed directly via it's Project DOI: 10.21228/M8TD9W This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001794 |
| Project DOI: | doi: 10.21228/M8TD9W |
| Project Title: | Comparative multi-omics analyses of cardiac mitochondrial stress in three mouse models of frataxin deficiency |
| Project Summary: | Cardiomyopathy is often fatal in Friedreich Ataxia (FA). However, the FA heart maintains adequate function until disease end stage, suggesting that it can initially adapt to the loss of frataxin (FXN). Conditional knockout mouse models with no Fxn expression show transcriptional and metabolic profiles of cardiomyopathy and mitochondrial integrated stress response (ISRmt). However, ISRmt has not been investigated in models with disease-relevant, partial decrease of FXN. We characterized the heart transcriptomes and metabolomes of three mouse models of partial FXN loss, YG8-800, KIKO-700, and FxnG127V. Few metabolites were significantly changed in YG8-800 mice and did not provide a signature of cardiomyopathy or ISRmt. Instead, several metabolites were altered in FxnG127V and KIKO-700 hearts. 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. |
| Institute: | Weill Cornell Medicine |
| Last Name: | Nicole |
| First Name: | Sayles |
| Address: | 407 East 61st St, 5th Floor, New York, NY 10065 |
| Email: | nms2009@med.cornell.edu |
| Phone: | 5167435432 |
| Publications: | https://journals.biologists.com/dmm/article/doi/10.1242/dmm.050114/328282/Comparative-multi-omics-analyses-of-cardiac |
Summary of all studies in project PR001794
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002872 | Comparative multi-omics analyses of cardiac mitochondrial stress in three mouse models of frataxin deficiency | Mus musculus | Weill Cornell Medicine | MS | 2023-09-28 | 1 | 26 | Uploaded data (469.2M)* |
