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.”
From Newer Gene Editing Technologies toward HIV Gene Therapy (2013) · cites this paper as [14]
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Self-citationAltering the Genome by Homologous Recombination
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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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Wnt signaling: a common theme in animal development
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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