A bestiary of genetic mouse lines and related tools for inducible and reversible intersectional misexpression
| Autor: | Aditi Singh, Daniel Stephen, Alberto Roselló-Díez, Alexandra L. Joyner, Elham Ahmadzadeh, Xinli Qu, Nermin Sumru Bayin, Linda Madisen, Hongkui Zeng |
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| Přispěvatelé: | Joyner, Alexandra L [0000-0001-7090-9605], Rosello-Diez, Alberto [0000-0002-5550-9846], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
tox176
Male Cell type animal structures Inducible and reversible gene mis-expression Transcription Genetic Transgene Gene Expression Locus (genetics) Mice Transgenic Computational biology Chick Embryo Biology 03 medical and health sciences Mice Techniques and Resources 0302 clinical medicine Ccn2/Ctgf Cerebellum Gene expression Animals Transgenes Enhancer Promoter Regions Genetic Molecular Biology Gene tTA DRAGON 030304 developmental biology 0303 health sciences p21 Tissue-specific Gene Transfer Techniques Embryo Cre Extremities DTA CTGF Disease Models Animal Gene Expression Regulation Doxycycline Trans-Activators Female Diphtheria toxin Intersectional genetics 030217 neurology & neurosurgery Developmental Biology Tigre locus rtTA |
| Zdroj: | Development |
| DOI: | 10.1101/754192 |
| Popis: | 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 utilizing 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 utilizes available lines expressing tTA/rTA to control 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.Summary statementAhmadzadeh et al. present a collection of four mouse lines and genetic tools for misexpression-mediated manipulation of cellular activity with high spatiotemporal control, in a reversible manner. |
| Databáze: | OpenAIRE |
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