ArticleProceedings of the National Academy of Sciences of the United States of America2013
Conditionals by inversion provide a universal method for the generation of conditional alleles.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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53 citing papers in PubMed.
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- Conditional replacement of the mouse LH receptor with GFP, enabling imaging of cell migration during ovulation.bioRxiv : the preprint server for biology · 2026Article
- Non-coding RNAs in lipid metabolism and their roles in atherosclerosis.Nature reviews. Cardiology · 2026Review
- Sclerostin deficiency sensitizes white adipocytes to thermogenic signals that induce beiging in mice.Nature communications · 2026Article
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- Dysfunction of exhausted T cells is enforced by MCT11-mediated lactate metabolism.Nature immunology · 2024Article
- Impact of essential genes on the success of genome editing experiments generating 3313 new genetically engineered mouse lines.Scientific reports · 2024Article
- Gastrulation-stage gene expression inScience advances · 2024Article
- Skeletal phenotype amelioration in mucopolysaccharidosis VI requires intervention at the earliest stages of postnatal development.JCI insight · 2023Article
- Peroxisome proliferator activated receptor-γ in osteoblasts controls bone formation and fat mass by regulating sclerostin expression.iScience · 2023Article
- Entering, Linked with the Sphinx: Lysophosphatidic Acids Everywhere, All at Once, in the Oral System and Cancer.International journal of molecular sciences · 2023Review
- Sostdc1 Suppression in the Absence of Sclerostin Potentiates Anabolic Action of Cortical Bone in Mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023Article
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- Muc4 loss mitigates epidermal growth factor receptor activity essential for PDAC tumorigenesis.Oncogene · 2023Article
- Review
- A neuronal action of sirtuin 1 suppresses bone mass in young and aging mice.The Journal of clinical investigation · 2022Article
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- SCON-a Short Conditional intrON for conditional knockout with one-step zygote injection.Experimental & molecular medicine · 2022Article
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34 authors.
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Abstract
Conditional mutagenesis is becoming a method of choice for studying gene function, but constructing conditional alleles is often laborious, limited by target gene structure, and at times, prone to incomplete conditional ablation. To address these issues, we developed a technology termed conditionals by inversion (COIN). Before activation, COINs contain an inverted module (COIN module) that lies inertly within the antisense strand of a resident gene. When inverted into the sense strand by a site-specific recombinase, the COIN module causes termination of the target gene's transcription and simultaneously provides a reporter for tracking this event. COIN modules can be inserted into natural introns (intronic COINs) or directly into coding exons as part of an artificial intron (exonic COINs), greatly simplifying allele design and increasing flexibility over previous conditional KO approaches. Detailed analysis of over 20 COIN alleles establishes the reliability of the method and its broad applicability to any gene, regardless of exon-intron structure. Our extensive testing provides rules that help ensure success of this approach and also explains why other currently available conditional approaches often fail to function optimally. Finally, the ability to split exons using the COIN's artificial intron opens up engineering modalities for the generation of multifunctional alleles.
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