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
-
- Animals, Genetically Modified/genetics*
- Genes, Switch*
- Transgenes*
- Animals
- Gene Transfer Techniques*
- PubMed
- 34916605 Full text @ Commun Biol
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