Related Experiment Video
Updated: Aug 17, 2025
In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
Vitamin B5, a coenzyme A precursor, rescues TANGO2 deficiency disease-associated defects in Drosophila and human
Paria Asadi1, Miroslav P Milev1, Djenann Saint-Dic1
1Department of Biology, Concordia University, Montreal, Quebec, Canada.
Abstract:
Mutations in the Transport and Golgi Organization 2 (TANGO2) gene are associated with intellectual deficit, neurodevelopmental delay and regression. Individuals can also present with an acute metabolic crisis that includes rhabdomyolysis, cardiomyopathy, and cardiac arrhythmias, the latter of which are potentially lethal. While preventing metabolic crises has the potential to reduce mortality, no treatments currently exist for this condition. The function of TANGO2 remains unknown but is suspected to be involved in some aspect of lipid metabolism. Here, we describe a model of TANGO2-related disease in the fruit fly Drosophila melanogaster that recapitulates crucial disease traits. Pairing a new fly model with human cells, we examined the effects of vitamin B5, a coenzyme A (CoA) precursor, on alleviating the cellular and organismal defects associated with TANGO2 deficiency. We demonstrate that vitamin B5 specifically improves multiple defects associated with TANGO2 loss-of-function in Drosophila and rescues membrane trafficking defects in human cells. We also observed a partial rescue of one of the fly defects by vitamin B3, though to a lesser extent than vitamin B5. Our data suggest that a B complex supplement containing vitamin B5/pantothenate may have therapeutic benefits in individuals with TANGO2-deficiency disease. Possible mechanisms for the rescue are discussed that may include restoration of lipid homeostasis.
Insights
Mutations in the Transport and Golgi Organization 2 (TANGO2) gene cause severe neurodevelopmental issues. Vitamin B5 (pantothenate) shows promise in alleviating TANGO2 deficiency symptoms, potentially by restoring lipid balance.
Area of Science:
- Genetics
- Neurobiology
- Metabolic Disorders
Background:
- Transport and Golgi Organization 2 (TANGO2) gene mutations are linked to intellectual disability, neurodevelopmental delays, and life-threatening metabolic crises.
- TANGO2 protein function is largely unknown but hypothesized to involve lipid metabolism, crucial for cellular processes.
- Currently, no effective treatments exist for TANGO2-deficiency disease, highlighting the need for therapeutic strategies.
Purpose of the Study:
- To develop and characterize a TANGO2-deficiency disease model in Drosophila melanogaster.
- To investigate the therapeutic potential of vitamin B5 (pantothenate) and other B vitamins in alleviating TANGO2-related cellular and organismal defects.
- To explore the underlying mechanisms by which vitamin B5 may rescue TANGO2 loss-of-function phenotypes.
Main Methods:
- Established a TANGO2 loss-of-function model in Drosophila melanogaster to mimic human disease traits.
- Utilized human cell lines to assess the impact of TANGO2 deficiency and vitamin B5 treatment on cellular functions.
- Administered vitamin B5 (pantothenate) and vitamin B3 to TANGO2-deficient flies and human cells to evaluate rescue effects.
Main Results:
- The Drosophila model successfully recapitulated key features of TANGO2-related disease.
- Vitamin B5 significantly improved multiple defects in TANGO2-deficient flies, including organismal and cellular phenotypes.
- Vitamin B5 rescued membrane trafficking abnormalities in human cells lacking functional TANGO2.
- Vitamin B3 demonstrated a partial rescue effect on one fly phenotype, but less potent than vitamin B5.
Conclusions:
- Vitamin B5 (pantothenate) supplementation may offer therapeutic benefits for individuals with TANGO2-deficiency disease.
- The findings suggest a potential role for TANGO2 in lipid metabolism and highlight vitamin B5 as a promising intervention.
- Further research into the mechanisms, possibly involving lipid homeostasis restoration, is warranted to optimize therapeutic strategies.
More Related Videos
Related Concept Videos
02:32Exon Recombination
Exon shuffling follows “splice frame rules.” Each exon...
01:39Mitochondrial Precursor Proteins
Most of the mitochondrial...