IQ-Switch is a QF-based innocuous, silencing-free, and inducible gene switch system in zebrafish.
Commun Biol
; 4(1): 1405, 2021 12 16.
Article
em En
| MEDLINE
| ID: mdl-34916605
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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Peixe-Zebra
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Animais Geneticamente Modificados
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Genes de Troca
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Técnicas de Transferência de Genes
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Transgenes
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article