ArticlePLoS genetics2008
An inducible and reversible mouse genetic rescue system.
Article in PLoS genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
51 citing papers in PubMed.
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- Comprehensive spatiotemporal mapping of single-cell lineages in developing mouse brain by CRISPR-based barcoding.Nature methods · 2023Article
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- Genetic and Molecular Quality Control of Genetically Engineered Mice.Methods in molecular biology (Clifton, N.J.) · 2023Article
- The impact of hepatocyte-specific deletion of hypoxia-inducible factors on the development of polymicrobial sepsis with focus on GR and PPARα function.Frontiers in immunology · 2023Article
- Genetic quality: a complex issue for experimental study reproducibility.Transgenic research · 2022Review
- Single-cell profiling of transcriptome and histone modifications with EpiDamID.Molecular cell · 2022Article
- Fluorescent protein transgenic mice for the study of CaFree radical biology & medicine · 2022Review
- Voltage imaging in the olfactory bulb using transgenic mouse lines expressing the genetically encoded voltage indicator ArcLight.Scientific reports · 2022Article
- Fluorescent transgenic mouse models for whole-brain imaging in health and disease.Frontiers in molecular neuroscience · 2022Review
- Microinjection of Zygotes for CRISPR/Cas9-Mediated Insertion of Transgenes into the Murine Rosa26 Safe Harbor.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Enzyme Replacement Therapy for Succinic Semialdehyde Dehydrogenase Deficiency: Relevance in γ-Aminobutyric Acid Plasticity.Journal of child neurology · 2021Article
- Lighting Up CaCells · 2021Review
- Distinct PRC2 subunits regulate maintenance and establishment of Polycomb repression during differentiation.Molecular cell · 2021Article
- Article
Corrections and comments
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Authors and funding
19 authors.
Funding
Abstract
Inducible and reversible regulation of gene expression is a powerful approach for uncovering gene function. We have established a general method to efficiently produce reversible and inducible gene knockout and rescue in mice. In this system, which we named iKO, the target gene can be turned on and off at will by treating the mice with doxycycline. This method combines two genetically modified mouse lines: a) a KO line with a tetracycline-dependent transactivator replacing the endogenous target gene, and b) a line with a tetracycline-inducible cDNA of the target gene inserted into a tightly regulated (TIGRE) genomic locus, which provides for low basal expression and high inducibility. Such a locus occurs infrequently in the genome and we have developed a method to easily introduce genes into the TIGRE site of mouse embryonic stem (ES) cells by recombinase-mediated insertion. Both KO and TIGRE lines have been engineered for high-throughput, large-scale and cost-effective production of iKO mice. As a proof of concept, we have created iKO mice in the apolipoprotein E (ApoE) gene, which allows for sensitive and quantitative phenotypic analyses. The results demonstrated reversible switching of ApoE transcription, plasma cholesterol levels, and atherosclerosis progression and regression. The iKO system shows stringent regulation and is a versatile genetic system that can easily incorporate other techniques and adapt to a wide range of applications.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.