Zinc finger (ZF) proteins belonging to the Cys2-His2 class provide a simple and versatile framework to design novel artificial transcription factors (ATFs) targeted to the desired genes. Our work is based on ZF ATFs engineered to up-regulate the expression level of the dystrophin-related gene utrophin in Duchenne muscular dystrophy (DMD). In particular, on the basis of the "recognition code" that defines specific rules between zinc finger primary structure and potential DNA-binding sites we engineered and selected a new family of artificial transcription factors, whose DNA-binding domain consists in a three zinc finger peptide called "Jazz." Jazz protein binds specifically the 9 bp DNA sequence (5′-GCT-GCT-GCG-3′) present in the promoter region of both the human and mouse utrophin gene. We generated a transgenic mouse expressing Jazz protein fused to the strong transcriptional activation domain VP16 and under the control of the muscle specific promoter of the myosin light chain gene. Vp16-Jazz mice display a strong up-regulation of the utrophin at both mRNA and protein levels. To our knowledge, this represents the first example of a transgenic mouse expressing an artificial gene coding for a zinc finger-based transcription factor. © 2010 Springer Science+Business Media, LLC.
CITATION STYLE
Passananti, C., Corbi, N., Onori, A., Di Certo, M. G., & Mattei, E. (2010). Transgenic mice expressing an artificial zinc finger regulator targeting an endogenous gene. Methods in Molecular Biology, 649, 183–206. https://doi.org/10.1007/978-1-60761-753-2_11
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