Summary of project PR001545
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 PR001545. The data can be accessed directly via it's Project DOI: 10.21228/M8099D This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001545 |
| Project DOI: | doi: 10.21228/M8099D |
| Project Title: | Lipidomics of Tango2 Deficient and Wildtype Zebrafish Muscle Tissue |
| Project Type: | Untargeted LC-MS/MS Lipidomics |
| Project Summary: | Rhabdomyolysis is a clinical emergency characterized by severe muscle damage, resulting in the release of intracellular muscle components which leads to myoglobinuria and in severe cases, acute kidney failure. Rhabdomyolysis is caused by genetic factors that are linked to increased disease susceptibility in response to extrinsic triggers. Recessive mutations in TANGO2 result in episodic rhabdomyolysis, metabolic crises, encephalopathy, and cardiac arrhythmia. The underlying mechanism contributing to disease onset in response to specific triggers remains unclear. To address these challenges, we created a zebrafish model of Tango2 deficiency. Here we demonstrate that the loss of Tango2 in zebrafish results in growth defects, early lethality, and increased susceptibility of muscle defects similar to TANGO2 patients. Detailed analyses of skeletal muscle revealed defects in the sarcoplasmic reticulum and mitochondria at the onset of disease development. The sarcoplasmic reticulum (SR) constitutes the primary lipid biosynthesis site and regulates calcium handling in skeletal muscle to control excitation-contraction coupling. Tango2 deficient SR exhibits increased sensitivity to calcium release that was partly restored by inhibition of Ryr1-mediated Ca2+ release in skeletal muscle. Using lipidomics, we identified alterations in the glycerolipid state of tango2 mutants which is critical for membrane stability and energy balance. Therefore, these studies provide insight into key disease processes in Tango2 deficiency and have increased our understanding of the impacts of specific defects on predisposition to environmental triggers in TANGO2-related disorders. |
| Institute: | UNC Chapel Hill |
| Department: | Chemistry |
| Laboratory: | MS Core Laboratory |
| Last Name: | Wallace |
| First Name: | Emily |
| Address: | 131 South Rd, Chapel Hill, NC, 27514, USA |
| Email: | emdiane@email.unc.edu |
| Phone: | 7042453664 |
| Funding Source: | NIH R56AR077017 |
| Publications: | Glycerolipid defects in skeletal muscle contribute to rhabdomyolysis in Tango2 deficiency (submitted to eLife) |
Summary of all studies in project PR001545
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002398 | Lipidomics of Tango2 Deficient and Wildtype Zebrafish Muscle Tissue | Danio rerio | University of North Carolina at Chapel Hill | MS | 2022-12-30 | 1 | 10 | Uploaded data (242.4M)* |
