A collection of genetic mouse lines and related tools for inducible and reversible intersectional mis-expression

Elham Ahmadzadeh, N. Sumru Bayin, Xinli Qu, Aditi Singh, Linda Madisen, Daniel Stephen, Hongkui Zeng, Alexandra L. Joyner, Alberto Rosello-Diez

Research output: Contribution to journalArticleResearchpeer-review

11 Citations (Scopus)

Abstract

Thanks to many advances in genetic manipulation, mouse models have become very powerful in their ability to interrogate biological processes. In order to precisely target expression of a gene of interest to particular cell types, intersectional genetic approaches using two promoter/enhancers unique to a cell type are ideal. Within these methodologies, variants that add temporal control of gene expression are the most powerful. We describe the development, validation and application of an intersectional approach that involves three transgenes, requiring the intersection of two promoter/enhancers to target gene expression to precise cell types. Furthermore, the approach uses available lines expressing tTA/rTA to control the timing of gene expression based on whether doxycycline is absent or present, respectively. We also show that the approach can be extended to other animal models, using chicken embryos. We generated three mouse lines targeted at the Tigre (Igs7) locus with TRE-loxP-tdTomato-loxP upstream of three genes (p21, DTA and Ctgf), and combined them with Cre and tTA/rtTA lines that target expression to the cerebellum and limbs. Our tools will facilitate unraveling biological questions in multiple fields and organisms.

Original languageEnglish
Article number186650
Number of pages12
JournalDevelopment
Volume147
Issue number10
DOIs
Publication statusPublished - May 2020

Keywords

  • Ccn2/Ctgf
  • Cre
  • Diphtheria toxin
  • DRAGON
  • DTA
  • Inducible and reversible gene mis-expression
  • Intersectional genetics
  • p21
  • rtTA
  • Tigre locus
  • Tissue-specific
  • tox176
  • tTA

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