The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
Targeted disruption of the murine int-1 proto-oncogene resulting in severe abnormalities in midbrain and cerebellar development
Abstract
The int-1 proto-oncogene was first identified as a gene activated in virally induced mouse mammary tumours. Expression studies, however, suggest that the normal function of this gene may be in spermatogenesis and in the development of the central nervous system. Genes sharing sequence similarity with int-1 have been found throughout the animal kingdom. For example, int-1 has 54% amino-acid identity to the Drosophila segment polarity gene wingless (wg). Both the int-1 and wg gene products seem to be secreted proteins, presumably involved in cell-cell signalling. We have now explored the function of int-1 in the mouse by disrupting one of the two int-1 alleles in mouse embryo-derived stem cells using positive-negative selection. This cell line was used to generate a chimaeric mouse that transmitted the mutant allele to its progeny. Mice heterozygous for the int-1 null mutation are normal and fertile, whereas mice homozygous for the mutation may exhibit a range of phenotypes from death before birth to survival with severe ataxia. The latter pathology in mice and humans is often associated with defects in the cerebellum. Examination of int-1-/int-1- mice at several stages of embryogenesis revealed severe abnormalities in the development of the mesencephalon and metencephalon indicating a prominent role for the int-1 protein is in the induction of the mesencephalon and cerebellum.
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“However, due to the extremely low frequency of HR, this technique cannot be used for human gene therapy.”
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Cites
Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells
Thomas, K. R., & Capecchi, M. R. (1987) · Cell · doi:10.1016/0092-8674(87)90646-5 · Cited by 2,355
Self-citationAltering the Genome by Homologous Recombination
Capecchi, M. R. (1989) · Science · doi:10.1126/science.2660260 · Cited by 2,037
Self-citationNusse, R., & VARMUS, H. E. (1982) · Cell · doi:10.1016/0092-8674(82)90409-3 · Cited by 1,864
Mansour, S. L., Thomas, K. R., & Capecchi, M. R. (1988) · Nature · doi:10.1038/336348a0 · Cited by 1,683
Self-citationDeChiara, T. M., Efstratiadis, A., & Robertsen, E. J. (1990) · Nature · doi:10.1038/345078a0 · Cited by 1,663
Formation of germ-line chimaeras from embryo-derived teratocarcinoma cell lines
Bradley, A., Evans, M. J., Kaufman, M. H., & Robertson, E. J. (1984) · Nature · doi:10.1038/309255a0 · Cited by 1,524
β2-Microglobulin deficient mice lack CD4−8+ cytolytic T cells
Zijlstra, M., Bix, M., Simister, N. E., Loring, J. M., Raulet, D. H., & Jaenisch, R. (1990) · Nature · doi:10.1038/344742a0 · Cited by 1,009
Rijsewijk, F. A. M., Schuermann, M., Wagenaar, E., Parren, P. W. H. I., Weigel, D., & Nusse, R. (1987) · Cell · doi:10.1016/0092-8674(87)90038-9 · Cited by 931
Normal Development of Mice Deficient in β 2 M, MCClass I Proteins, and CD8 + T Cells
Koller, B. H., Marrack, P., Kappler, J. W., & Smithies, O. (1990) · Science · doi:10.1126/science.2112266 · Cited by 884
The new mouse genetics: Altering the genome by gene targeting
Capecchi, M. R. (1989) · Trends in Genetics · doi:10.1016/0168-9525(89)90029-2 · Cited by 611
Self-citationWilkinson, D. G., Bailes, J. A., & McMahon, A. P. (1987) · Cell · doi:10.1016/0092-8674(87)90664-7 · Cited by 568
Baker, N. E. (1987) · The EMBO Journal · doi:10.1002/j.1460-2075.1987.tb02429.x · Cited by 436
Zijlstra, M., Li, E., Sajjadi, F., Subramani, S., & Jaenisch, R. (1989) · Nature · doi:10.1038/342435a0 · Cited by 347
A new approach to the development of the cerebellum provided by the quail–chick marker system
Hallonet, M. E. R., Teillet, M., & Douarin, N. M. L. (1990) · Development · doi:10.1242/dev.108.1.19 · Cited by 301
Germ-Line Transmission of a c- abl Mutation Produced by Targeted Gene Disruption in ES Cells
Schwartzberg, P. L., Goff, S. P., & Robertson, E. J. (1989) · Science · doi:10.1126/science.2554496 · Cited by 272
The proto‐oncogene int‐1 encodes a secreted protein associated with the extracellular matrix.
Bradley, R. S., & Brown, A. M. C. (1990) · The EMBO Journal · doi:10.1002/j.1460-2075.1990.tb08276.x · Cited by 269
Shackleford, G. M., & VARMUS, H. E. (1987) · Cell · doi:10.1016/0092-8674(87)90665-9 · Cited by 246
van Ooyen, A., & Nusse, R. (1984) · Cell · doi:10.1016/0092-8674(84)90209-5 · Cited by 224
Koller, B. H., & Smithies, O. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.22.8932 · Cited by 216
Targeted mutation of the Hprt gene in mouse embryonic stem cells.
Doetschman, T., Maeda, N., & Smithies, O. (1988) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.85.22.8583 · Cited by 212
Secreted int-1 Protein Is Associated with the Cell Surface
Papkoff, J. S., & Schryver, B. B. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.6.2723 · Cited by 210
Jakobovits, A., Shackleford, G. M., VARMUS, H. E., & Martin, G. R. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.20.7806 · Cited by 206
Production of a mutation in mouse En-2 gene by homologous recombination in embryonic stem cells
Joyner, A. L., Skarnes, W. C., & Rossant, J. (1989) · Nature · doi:10.1038/338153a0 · Cited by 195
The development of wingless, a homeotic mutation of Drosophila
Morata, G., & Lawrence, P. A. (1977) · Developmental Biology · doi:10.1016/0012-1606(77)90266-4 · Cited by 188
Zimmer, A., & Gruß, P. (1989) · Nature · doi:10.1038/338150a0 · Cited by 161
The int -1 Proto-Oncogene Products Are Glycoproteins That Appear To Enter the Secretory Pathway
Papkoff, J. S., Brown, A. M., & VARMUS, H. E. (1987) · Molecular and Cellular Biology · doi:10.1128/mcb.7.11.3978-3984.1987 · Cited by 145
Targeting of Nonexpressed Genes in Embryonic Stem Cells Via Homologous Recombination
Johnson, R. S., Sheng, M., Greenberg, M. E., Kolodner, R. D., Papaioannou, V. E., & Spiegelman, B. M. (1989) · Science · doi:10.1126/science.2506639 · Cited by 104
The int-1 proto-oncogene products are glycoproteins that appear to enter the secretory pathway.
Papkoff, J., Brown, A. M., & VARMUS, H. E. (1987) · Molecular and Cellular Biology · doi:10.1128/mcb.7.11.3978 · Cited by 92
Towards a molecular-genetic analysis of mammalian development
Rossant, J., & Joyner, A. L. (1989) · Trends in Genetics · doi:10.1016/0168-9525(89)90102-9 · Cited by 73
Schwartzberg, P. L., Robertson, E. J., & Goff, S. P. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.8.3210 · Cited by 64
Fell, H. P., Yarnold, S., Hellström, I., Hellström, K. E., & Folger, K. R. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.21.8507 · Cited by 61
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- Mansour, S. L., Thomas, K. R., Deng, C. & Capecchi, M. R. Proc. natn. Acad. Sci. U.S.A. (in the press).
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Cadigan, K. M., & Nusse, R. (1997) · Genes & Development · doi:10.1101/gad.11.24.3286 · Cited by 2,567
Echelard, Y., Epstein, D. J., St-Jacques, B., Shen, L., Mohler, J., McMahon, J. A., & McMahon, A. P. (1993) · Cell · doi:10.1016/0092-8674(93)90627-3 · Cited by 2,154
MECHANISMS OF WNT SIGNALING IN DEVELOPMENT
Wodarz, A., & Nusse, R. (1998) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.14.1.59 · Cited by 2,030
Wnt signalling and its impact on development and cancer
Klaus, A., & Birchmeier, W. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2389 · Cited by 1,595
Stem Cells in the Central Nervous System
McKay, R. D. G. (1997) · Science · doi:10.1126/science.276.5309.66 · Cited by 1,475
Metadata
- Authors
- Thomas, K. R., & Capecchi, M. R.
- Affiliations
- Howard Hughes Medical Institute (US)
- ORCID
- Capecchi, Mario R.
- Venue
- Nature
- Published
- 1990-08
- Volume
- 346
- Issue
- 6287
- Pages
- 847-850
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2033291406
- Cited by
- 896
- References
- 30
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 8 · 2023: 14 · 2022: 10 · 2021: 13 · 2020: 19 · 2019: 9 · 2018: 6 · 2017: 18 · 2016: 20 · 2015: 20 · 2014: 12 · 2013: 35 · 2012: 26
- FWCI
- 23.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Keywords
- cerebellar development, midbrain development, metencephalon, ataxia, cell-to-cell communication, chimeric mice, embryonic stem cells, spermatogenesis
- MeSH terms
- Proto-Oncogene Mas, Animals, Blastocyst, Cell Line, Cerebellum, Chimera, DNA, Female, Genotype, Heterozygote, Homozygote, Male, Mesencephalon, Mice, Inbred C57BL, Motor Activity, Mutation, Nucleic Acid Hybridization, Proto-Oncogene Proteins, Stem Cells, Transfection, Zebrafish Proteins, Wnt Proteins, Wnt1 Protein, Mice
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