PUBLICATION
Intrinsic and extrinsic regulation of rhabdomyolysis susceptibility by Tango2
- Authors
- Kim, E.S., Casey, J.G., Tao, B.S., Mansur, A., Mathiyalagan, N., Wallace, E.D., Ehrmann, B.M., Gupta, V.A.
- ID
- ZDB-PUB-230814-51
- Date
- 2023
- Source
- Disease models & mechanisms 16(9): (Journal)
- Registered Authors
- Gupta, Vandana A
- Keywords
- Lipid homeostasis, Rhabdomyolysis, Skeletal Muscle, Zebrafish
- MeSH Terms
-
- Animals
- Energy Metabolism
- Muscle, Skeletal
- Mutation/genetics
- Rhabdomyolysis*/complications
- Rhabdomyolysis*/genetics
- Zebrafish*
- PubMed
- 37577943 Full text @ Dis. Model. Mech.
Citation
Kim, E.S., Casey, J.G., Tao, B.S., Mansur, A., Mathiyalagan, N., Wallace, E.D., Ehrmann, B.M., Gupta, V.A. (2023) Intrinsic and extrinsic regulation of rhabdomyolysis susceptibility by Tango2. Disease models & mechanisms. 16(9):.
Abstract
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 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 skeletal muscle defects in response to extrinsic triggers similar to TANGO2 patients. Using lipidomics, we identified alterations in the glycerolipid pathway in 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping