ArticleGenome biology2020
Genes adapt to outsmart gene-targeting strategies in mutant mouse strains by skipping exons to reinitiate transcription and translation.
Article in Genome biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 37 citations in OpenAlex.
- Molecular characterization of Cdh12-SCON conditional knockout mice reveals unexpected splicing changes.Transgenic research · 2026Article
- A sterol-binding pocket in iRhom1 underlies paralog-specific regulation of the sheddase ADAM17.bioRxiv : the preprint server for biology · 2026Article
- tRNA-based polycistronic CRISPR/Cas9 system boosts efficiency of multi-gene deletion in the moss Physcomitrella.Plant methods · 2026Article
- Holding Out for a Model: Rhomboid Superfamily in Vertebrate Development and Disease.Journal of cellular physiology · 2025Review
- Translational Control in Cardiac Pathophysiology and Therapeutic Development: When mRNA Meets the Heart.International journal of molecular sciences · 2025Review
- Systematic optimization and prediction of cre recombinase for precise genome editing in mice.Genome biology · 2025Article
- SelectRepair Knockout: Efficient PTC-Free Gene Knockout Through Selectable Homology-Directed DNA Repair.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Investigating the effects of a cryptic splice site in the En2 splice acceptor sequence used in the IKMC knockout-first alleles.Mammalian genome : official journal of the International Mammalian Genome Society · 2024Article
- Loss-of-function of RNA-binding protein PRRC2B causes translational defects and congenital cardiovascular malformation.medRxiv : the preprint server for health sciences · 2024Article
- Large-Scale Genome-Wide Optimization and Prediction of the Cre Recombinase System for Precise Genome Manipulation in Mice.Research square · 2024Article
- Large-Scale Genome-Wide Optimization and Prediction of the Cre Recombinase System for Precise Genome Manipulation in Mice.bioRxiv : the preprint server for biology · 2024Article
- CRIMP: a CRISPR/Cas9 insertional mutagenesis protocol and toolkit.Nature communications · 2024Article
- Identification of high-performing antibodies for the reliable detection of Tau proteoforms by Western blotting and immunohistochemistry.Acta neuropathologica · 2024Article
- Escaping from CRISPR-Cas-mediated knockout: the facts, mechanisms, and applications.Cellular & molecular biology letters · 2024Review
- Analysis of the function of ADAM17 in iRhom2 curly-bare and tylosis with esophageal cancer mutant mice.Journal of cell science · 2023Article
- Comprehensive behavioral analyses of mice with a glycine receptor alpha 4 deficiency.Molecular brain · 2023Article
- Karyopherin α deficiency contributes to human preimplantation embryo arrest.The Journal of clinical investigation · 2023Article
- Loss of mouse Y chromosome gene Zfy1 and Zfy2 leads to spermatogenesis impairment, sperm defects, and infertility.Biology of reproduction · 2022Article
- Screening and validation of genome-edited animals.Laboratory animals · 2022Article
- Inactive rhomboid proteins RHBDF1 and RHBDF2 (iRhoms): a decade of research in murine models.Mammalian genome : official journal of the International Mammalian Genome Society · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundGene disruption in mouse embryonic stem cells or zygotes is a conventional genetics approach to identify gene function in vivo. However, because different gene disruption strategies use different mechanisms to disrupt genes, the strategies can result in diverse phenotypes in the resulting mouse model. To determine whether different gene disruption strategies affect the phenotype of resulting mutant mice, we characterized Rhbdf1 mouse mutant strains generated by three commonly used strategies-definitive-null, targeted knockout (KO)-first, and CRISPR/Cas9.
resultsWe find that Rhbdf1 responds differently to distinct KO strategies, for example, by skipping exons and reinitiating translation to potentially yield gain-of-function alleles rather than the expected null or severe hypomorphic alleles. Our analysis also revealed that at least 4% of mice generated using the KO-first strategy show conflicting phenotypes.
conclusionsExon skipping is a widespread phenomenon occurring across the genome. These findings have significant implications for the application of genome editing in both basic research and clinical practice.
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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.