PUBLICATION
IQ-Switch is a QF-based innocuous, silencing-free, and inducible gene switch system in zebrafish
- Authors
- Hong, J., Lee, J.G., Sohn, K.C., Lee, K., Lee, S., Lee, J., Hong, J., Choi, D., Hong, Y., Jin, H.S., Choi, D.K., Lee, S.U., Kee, Y., Jung, J., Bae, Y.K., Hwang, R.H., Hur, G.M., Lee, J.S., Ro, H.
- ID
- ZDB-PUB-211221-4
- Date
- 2021
- Source
- Communications biology 4: 1405 (Journal)
- Registered Authors
- Bae, Young Ki, Kee, Yun, Lee, Jeong-Soo, Lee, Seoee, Ro, Hyunju
- Keywords
- none
- MeSH Terms
-
- Gene Transfer Techniques*
- Transgenes*
- Animals, Genetically Modified/genetics*
- Genes, Switch*
- Zebrafish/genetics*
- Animals
- PubMed
- 34916605 Full text @ Commun Biol
Citation
Hong, J., Lee, J.G., Sohn, K.C., Lee, K., Lee, S., Lee, J., Hong, J., Choi, D., Hong, Y., Jin, H.S., Choi, D.K., Lee, S.U., Kee, Y., Jung, J., Bae, Y.K., Hwang, R.H., Hur, G.M., Lee, J.S., Ro, H. (2021) IQ-Switch is a QF-based innocuous, silencing-free, and inducible gene switch system in zebrafish. Communications biology. 4:1405.
Abstract
Though various transgene expression switches have been adopted in a wide variety of organisms for basic and biomedical research, intrinsic obstacles of those existing systems, including toxicity and silencing, have been limiting their use in vertebrate transgenesis. Here we demonstrate a novel QF-based binary transgene switch (IQ-Switch) that is relatively free of driver toxicity and transgene silencing, and exhibits potent and highly tunable transgene activation by the chemical inducer tebufenozide, a non-toxic lipophilic molecule to developing zebrafish with negligible background. The interchangeable IQ-Switch makes it possible to elicit ubiquitous and tissue specific transgene expression in a spatiotemporal manner. We generated a RASopathy disease model using IQ-Switch and demonstrated that the RASopathy symptoms were ameliorated by the specific BRAF(V600E) inhibitor vemurafenib, validating the therapeutic use of the gene switch. The orthogonal IQ-Switch provides a state-of-the-art platform for flexible regulation of transgene expression in zebrafish, potentially applicable in cell-based systems and other model organisms.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping