ArticleArteriosclerosis, thrombosis, and vascular biology2015
CRISPR-Cas9 genome editing of a single regulatory element nearly abolishes target gene expression in mice--brief report.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 55 citations in OpenAlex.
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- Genetic Modification of Mice Using Prime Editing.Current protocols · 2024Article
- Prime editing in mice with an engineered pegRNA.Vascular pharmacology · 2024Article
- Calponin 1 inhibits agonist-induced ERK activation and decreases calcium sensitization in vascular smooth muscle.Journal of cellular and molecular medicine · 2024Article
- Transgenesis and Genome Engineering: A Historical Review.Methods in molecular biology (Clifton, N.J.) · 2023Article
- CRISPR base editing of cis-regulatory elements enables the perturbation of neurodegeneration-linked genes.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Platr4 is an early embryonic lncRNA that exerts its function downstream on cardiogenic mesodermal lineage commitment.Developmental cell · 2022Article
- Prime editing in mice reveals the essentiality of a single base in driving tissue-specific gene expression.Genome biology · 2021Article
- Elimination ofRNA (New York, N.Y.) · 2020Article
- Coronary Disease-Associated GeneCirculation research · 2020Article
- Transcriptional control of a novel long noncoding RNA Mymsl in smooth muscle cells by a single Cis-element and its initial functional characterization in vessels.Journal of molecular and cellular cardiology · 2020Article
- Regulatory variants: from detection to predicting impact.Briefings in bioinformatics · 2019Review
- Genetic Insights Into Smooth Muscle Cell Contributions to Coronary Artery Disease.Arteriosclerosis, thrombosis, and vascular biology · 2019Review
- CRISPR links to long noncoding RNA function in mice: A practical approach.Vascular pharmacology · 2019Review
- Article
- Directed evolution studies of a thermophilic Type II-C Cas9.Methods in enzymology · 2019Article
- Phosphate Lock Residues of Acidothermus cellulolyticus Cas9 Are Critical to Its Substrate Specificity.ACS synthetic biology · 2018Article
- CRISPR-Cas9-Mediated Epitope Tagging Provides Accurate and Versatile Assessment of Myocardin-Brief Report.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
- Nexilin/NEXN controls actin polymerization in smooth muscle and is regulated by myocardin family coactivators and YAP.Scientific reports · 2018Article
- Review
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5 authors at 1 institution in 2 countries.
Funding
Abstract
objectiveTo ascertain the importance of a single regulatory element in the control of Cnn1 expression using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) genome editing. APPROACH AND
resultsThe CRISPR/Cas9 system was used to produce 3 of 18 founder mice carrying point mutations in an intronic CArG box of the smooth muscle cell-restricted Cnn1 gene. Each founder was bred for germline transmission of the mutant CArG box and littermate interbreeding to generate homozygous mutant (Cnn1(ΔCArG/ΔCArG)) mice. Quantitative reverse transcription polymerase chain reaction, Western blotting, and confocal immunofluorescence microscopy showed dramatic reductions in Cnn1 mRNA and CNN1 protein expression in Cnn1(ΔCArG/ΔCArG) mice with no change in other smooth muscle cell-restricted genes and little evidence of off-target edits elsewhere in the genome. In vivo chromatin immunoprecipitation assay revealed a sharp decrease in binding of serum response factor to the mutant CArG box. Loss of CNN1 expression was coincident with an increase in Ki-67 positive cells in the normal vessel wall.
conclusionsCRISPR/Cas9 genome editing of a single CArG box nearly abolishes Cnn1 expression in vivo and evokes increases in smooth muscle cell DNA synthesis. This facile genome editing system paves the way for a new generation of studies designed to test the importance of individual regulatory elements in living animals, including regulatory variants in conserved sequence blocks linked to human disease.
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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.