Abstract
Two recent developments suggest a route to predetermined alterations in mammalian germlines. These are, first, the characterization of mouse embryonic stem (ES) cells1 that can still enter the germline after genetic manipulation in culture2,3 and second, the demonstration that homologous recombination between a native target chromosomal gene and exogenous DNA can be used in culture to modify specifically the target locus4. We here use gene targetting functionally to correct the mutant hypoxanthine-guanine phosphoribosyl transferase (HPRT) gene in the ES cell line which has previously been isolated and used to produce an HPRT-deficient mouse5. This modification of a chosen gene in pluripotent ES cells demonstrates the feasibility of this route to manipulating mammalian genomes in predetermined ways.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
1. Evans, M. J. & Kaufman, M. H. Nature 292, 154–156 (1981). 2. Gossler, A., Doetschman, T., Korn, R., Serfling, E. & Kemler, R. Proc. natn. Acad. Sci.U.S.A. 83, 9065–9069 (1986). 3. Robertson, E., Bradley, A., Kuehn, M. & Evans, M. Nature 323, 445–448 (1986). 4. Smithies, O., Gregg, R. G., Boggs, S. S., Koralewski, M. A. & Kucherlapati, R. S. Nature 317, 230–234 (1985). 5. Hooper, M., Hardy, K., Handyside, A., Hunter, S. & Monk, M. Nature 326, 292–295 (1987). 6. Kuehn, M. R., Bradley, M., Robertson, E. J. & Evans, M. J. Nature 326, 295–298 (1987). 7. Smith, A. J. H. & Berg, P. Cold Spring Harb. Symp. quant. Biol. 149, 171–181 (1984). 8. Smithies, O., Koralewski, M. A., Song, K.-Y. & Kucherlapati, R. S. Cold Spring Harb. Symp. quant. Biol. 49, 161–170 (1984). 9. Lin, F.-L., Sperle, K. K. & Sternberg, N. Cold Spring Harb. Symp. quant. Biol. 49, 139–149 (1984). 10.Lin, F.-L., Sperle, K. & Sternberg, N. Proc. natn. Acad. Sci. U.S.A. 82, 1391–1395 (1985). 11.Rubnitz, J. & Subramani, S. Molec. cell. Biol. 6, 1608–1614 (1986). 12.Thomas, K. R., Folger, K. R. & Capecchi, M. R. Cell 44, 419–428 (1986). 13.Gregg, R. G. & Smithies, O. Cold Spring Harbor Symp. quant. Biol. 51, 1093–1099 (1986). 14.Song, K.-Y., Schwartz, F., Maeda, N., Smithies, O. & Kucherlapati, R. S. Proc. natn. Acad. Sci. U.S.A. 84, 6820–6824 (1987). 15.Boggs, S. S., Gregg, R. G., Borenstein, N. & Smithies, O. Expl Hemat. 14, 988–994 (1986). 16.Smith, A. G. & Hooper, M. L. Devl Biol. 121, 1–9 (1987). 17.Southern, P. J. & Berg, P. J. Molec. Appl. Genet. 1, 327–341 (1982). 18.Melton, D. W., Konecki, D. S., Brennand, J. & Caskey, C. T. Proc. natn. Acad. Sci. U.S.A. 81,2147–2151 (1984). 19.Ayares, D., Ganea, D., Chekuri, L., Campbell, C. R. & Kucherlapati, R. Molec. cell. Biol. 7, 1656–1662 (1987).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Doetschman, T., Gregg, R., Maeda, N. et al. Targetted correction of a mutant HPRT gene in mouse embryonic stem cells. Nature 330, 576–578 (1987). https://doi.org/10.1038/330576a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/330576a0
This article is cited by
-
Multi-feature clustering of CTCF binding creates robustness for loop extrusion blocking and Topologically Associating Domain boundaries
Nature Communications (2023)
-
3R measures in facilities for the production of genetically modified rodents
Lab Animal (2022)
-
Genetic quality: a complex issue for experimental study reproducibility
Transgenic Research (2022)
-
CRISPR somatic genome engineering and cancer modeling in the mouse pancreas and liver
Nature Protocols (2022)
-
From the T-cell receptor to cancer therapy: an interview with Tak W. Mak
Cell Death & Differentiation (2021)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.