ArticleNucleic acids research2015
Functional validation of mouse tyrosinase non-coding regulatory DNA elements by CRISPR-Cas9-mediated mutagenesis.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 76 citations in OpenAlex.
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- Integrative functional genomic analyses identify genetic variants influencing skin pigmentation in Africans.Nature genetics · 2024Article
- Affinity Purification of Intraflagellar Transport (IFT) Proteins in Mice Using Endogenous Streptavidin/FLAG Tags.Methods in molecular biology (Clifton, N.J.) · 2024Article
- A Slc38a8 Mouse Model of FHONDA Syndrome Faithfully Recapitulates the Visual Deficits of Albinism Without Pigmentation Defects.Investigative ophthalmology & visual science · 2023Article
- Sphk1 deficiency induces apoptosis and developmental defects and premature death in zebrafish.Fish physiology and biochemistry · 2023Article
- Transgenesis and Genome Engineering: A Historical Review.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Evolution of CRISPR-associated endonucleases as inferred from resurrected proteins.Nature microbiology · 2023Article
- CRISPR-Cas9-mediated functional dissection of the foxc1 genomic region in zebrafish identifies critical conserved cis-regulatory elements.Human genomics · 2022Article
- Role of animal models in biomedical research: a review.Laboratory animal research · 2022Review
- CRISPR/Cas9-Mediated Allele-Specific Disruption of a DominantInternational journal of molecular sciences · 2022Article
- Transcription factor-mediated intestinal metaplasia and the role of a shadow enhancer.Genes & development · 2022Article
- Historical DNA Manipulation Overview.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Toward precise CRISPR DNA fragment editing and predictable 3D genome engineering.Journal of molecular cell biology · 2021Review
- A holistic view of mouse enhancer architectures reveals analogous pleiotropic effects and correlation with human disease.BMC genomics · 2020Article
- Boundary sequences flanking the mouse tyrosinase locus ensure faithful pattern of gene expression.Scientific reports · 2020Article
- Article
- Review
- The Value of Mouse Models of Rare Diseases: A Spanish Experience.Frontiers in genetics · 2020Article
- WeReview: CRISPR Tools-Live Repository of Computational Tools for Assisting CRISPR/Cas Experiments.Bioengineering (Basel, Switzerland) · 2019Article
- Rational targeting of a NuRD subcomplex guided by comprehensive in situ mutagenesis.Nature genetics · 2019Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Newly developed genome-editing tools, such as the clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 system, allow simple and rapid genetic modification in most model organisms and human cell lines. Here, we report the production and analysis of mice carrying the inactivation via deletion of a genomic insulator, a key non-coding regulatory DNA element found 5' upstream of the mouse tyrosinase (Tyr) gene. Targeting sequences flanking this boundary in mouse fertilized eggs resulted in the efficient deletion or inversion of large intervening DNA fragments delineated by the RNA guides. The resulting genome-edited mice showed a dramatic decrease in Tyr gene expression as inferred from the evident decrease of coat pigmentation, thus supporting the functionality of this boundary sequence in vivo, at the endogenous locus. Several potential off-targets bearing sequence similarity with each of the two RNA guides used were analyzed and found to be largely intact. This study reports how non-coding DNA elements, even if located in repeat-rich genomic sequences, can be efficiently and functionally evaluated in vivo and, furthermore, it illustrates how the regulatory elements described by the ENCODE and EPIGENOME projects, in the mouse and human genomes, can be systematically validated.
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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.