Summary of Study ST002398

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.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002398
Study TitleLipidomics of Tango2 Deficient and Wildtype Zebrafish Muscle Tissue
Study TypeUntargeted Lipidomics
Study SummaryRhabdomyolysis 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
University of North Carolina at Chapel Hill
DepartmentChemistry
LaboratoryMS Core Laboratory
Last NameWallace
First NameEmily
Address131 South Rd
Emailemdiane@email.unc.edu
Phone7042453664
Submit Date2022-12-07
Num Groups2
Total Subjects5
Num MalesN/A
Num FemalesN/A
Study CommentsZebrafish were all 4 weeks old when tissue was harvested, sex is determined at 4 weeks old.
Raw Data AvailableYes
Raw Data File Type(s)mzXML
Analysis Type DetailLC-MS
Release Date2022-12-30
Release Version1
Emily Wallace Emily Wallace
https://dx.doi.org/10.21228/M8099D
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Factors:

Subject type: Fish; Subject species: Danio rerio (Factor headings shown in green)

mb_sample_id local_sample_id Genotype Weight (mg)
SA239045Z15tango2 Mutant 13.5
SA239046Z2tango2 Mutant 15
SA239047Z22tango2 Mutant 26
SA239048Z1tango2 Mutant 69.5
SA239049Z11tango2 Mutant 8
SA239040Z34Wildtype 17
SA239041Z25Wildtype 18.7
SA239042Z19Wildtype 20
SA239043Z20Wildtype 57.1
SA239044Z14Wildtype 9
Showing results 1 to 10 of 10
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