Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells
Abstract
We mutated, by gene targeting, the endogenous hypoxanthine phosphoribosyl transferase (HPRT) gene in mouse embryo-derived stem (ES) cells. A specialized construct of the neomycin resistance (neor) gene was introduced into an exon of a cloned fragment of the Hprt gene and used to transfect ES cells. Among the G418r colonies, 1/1000 were also resistant to the base analog 6-thioguanine (6-TG). The G418r, 6-TGr cells were all shown to be Hprt- as the result of homologous recombination with the exogenous, neor-containing, Hprt sequences. We have compared the gene-targeting efficiencies of two classes of neor-Hprt recombinant vectors: those that replace the endogenous sequence with the exogenous sequence and those that insert the exogenous sequence into the endogenous sequence. The targeting efficiencies of both classes of vectors are strongly dependent upon the extent of homology between exogenous and endogenous sequences. The protocol described herein should be useful for targeting mutations into any gene.
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Due to the extremely low frequency of homologous recombination, this technique cannot be used for human gene therapy.
“However, due to the extremely low frequency of HR, this technique cannot be used for human gene therapy.”
From Newer Gene Editing Technologies toward HIV Gene Therapy (2013) · cites this paper as [13]
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- Authors
- Thomas, K. R., & Capecchi, M. R.
- Affiliations
- University of Utah (US)
- ORCID
- Capecchi, Mario R.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1987-11
- Volume
- 51
- Issue
- 3
- Pages
- 503-512
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1993834457
- Cited by
- 2,355
- References
- 35
- Citations by year
- 2026: 11 · 2025: 21 · 2024: 27 · 2023: 31 · 2022: 40 · 2021: 50 · 2020: 55 · 2019: 46 · 2018: 49 · 2017: 47 · 2016: 61 · 2015: 74 · 2014: 51 · 2013: 69 · 2012: 71
- FWCI
- 17.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cystic Fibrosis Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- Tn10 transposon, transposon ends, type II restriction endonuclease, protein-DNA recognition, DNA cleavage, site-directed mutagenesis, gene targeting
- MeSH terms
- Animals, Blastocyst, Cells, Cultured, DNA Restriction Enzymes, Genes, Genetic Vectors, Hematopoietic Stem Cells, Hypoxanthine Phosphoribosyltransferase, Mice, Inbred C57BL, Mutation, Nucleic Acid Hybridization, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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