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  • Title: Disease modeling by gene targeting using microRNAs.
    Author: Lan CC, Leong IU, Lai D, Love DR.
    Journal: Methods Cell Biol; 2011; 105():419-36. PubMed ID: 21951541.
    Abstract:
    Zebrafish have proved to be a popular species for the modeling of human disease. In this context, there is a need to move beyond chemical-based mutagenesis and develop tools that target genes that are orthologous to those that are implicated in human heritable diseases. Targeting can take the form of creating mutations that are nonsense or mis-sense, or to mimic haploinsufficiency through the regulated expression of RNA effector molecules. In terms of the latter, we describe here the development and investigation of microRNA (miRNA)-based directed gene silencing methods in zebrafish. Unlike small interfering RNAs (siRNAs), miRNA-based methods offer temporal and spatial regulation of gene silencing. Proof-of-concept experiments demonstrate the efficacy of the method in zebrafish embryos, which provide the foundation for developing disease models using miRNA-based gene-targeting.
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