PUBLICATION
Effective heritable gene knockdown in zebrafish using synthetic microRNAs
- Authors
- Giacomotto, J., Rinkwitz, S., Becker, T.S.
- ID
- ZDB-PUB-150609-9
- Date
- 2015
- Source
- Nature communications 6: 7378 (Journal)
- Registered Authors
- Becker, Thomas S., Giacomotto, Jean, Rinkwitz, Silke
- Keywords
- Gene targeting, miRNAs, Neuromuscular disease, Zebrafish
- MeSH Terms
-
- Zebrafish/genetics*
- Animals
- 3' Untranslated Regions
- MicroRNAs/genetics*
- Zebrafish Proteins/genetics
- Animals, Genetically Modified
- Gene Knockdown Techniques*
- PubMed
- 26051838 Full text @ Nat. Commun.
Citation
Giacomotto, J., Rinkwitz, S., Becker, T.S. (2015) Effective heritable gene knockdown in zebrafish using synthetic microRNAs. Nature communications. 6:7378.
Abstract
Although zebrafish is used to model human diseases through mutational and morpholino-based knockdown approaches, there are currently no robust transgenic knockdown tools. Here we investigate the knockdown efficiency of three synthetic miRNA-expressing backbones and show that these constructs can downregulate a sensor transgene with different degrees of potency. Using this approach, we reproduce spinal muscular atrophy (SMA) in zebrafish by targeting the smn1 gene. We also generate different transgenic lines, with severity and age of onset correlated to the level of smn1 inhibition, recapitulating for the first time the different forms of SMA in zebrafish. These lines are proof-of-concept that miRNA-based approaches can be used to generate potent heritable gene knockdown in zebrafish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping