Transgenic mice expressing an artificial zinc finger regulator targeting an endogenous gene

Claudio Passananti, Nicoletta Corbi, Annalisa Onori, Maria Grazia Di Certo, Elisabetta Mattei

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

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.

Original languageEnglish
Title of host publicationMethods in Molecular Biology
Pages183-206
Number of pages24
Volume649
DOIs
Publication statusPublished - 2010

Publication series

NameMethods in Molecular Biology
Volume649
ISSN (Print)10643745

Keywords

  • artificial transcription factor
  • dystrophin
  • gene therapy
  • muscular dystrophy
  • synthetic gene
  • transgenic mice
  • utrophin
  • Zinc finger

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Medicine(all)

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