The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
tp53 mutant zebrafish develop malignant peripheral nerve sheath tumors
Open accessAbstract
TP53 is the most frequently mutated tumor suppressor gene in human cancer, with nearly 50% of all tumors exhibiting a loss-of-function mutation. To further elucidate the genetic pathways involving TP53 and cancer, we have exploited the zebrafish, a powerful vertebrate model system that is amenable to whole-genome forward-genetic analysis and synthetic-lethal screens. Zebrafish lines harboring missense mutations in the tp53 DNA-binding domain were identified by using a target-selected mutagenesis strategy. Homozygous mutant fish from two of these lines were viable and exhibited mutations similar to those found in human cancers ( tp53 N168K and tp53 M214K ). Although homozygous tp53 N168K mutants were temperature-sensitive and suppressed radiation-induced apoptosis only at 37°C, cells in the tp53 M214K embryos failed to undergo apoptosis in response to γ radiation at both 28 and 37°C. Unlike wild-type control embryos, irradiated tp53 M214K embryos also failed to up-regulate p21 and did not arrest at the G 1 /S checkpoint. Beginning at 8.5 months of age, 28% of tp53 M214K mutant fish developed malignant peripheral nerve sheath tumors. In addition to providing a model for studying the molecular pathogenic pathways of malignant peripheral nerve sheath tumors, these mutant zebrafish lines provide a unique platform for modifier screens to identify genetic mutations or small molecules that affect tp53 -related pathways, including apoptosis, cell-cycle delay, and tumor suppression.
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Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours
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Mice Lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control
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Cited by
Therapeutic targeting of p53: all mutants are equal, but some mutants are more equal than others
Sabapathy, K., & Lane, D. P. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.151 · Cited by 517
Effects of RAS on the genesis of embryonal rhabdomyosarcoma
Langenau, D. M., Keefe, M. D., Storer, N. Y., Guyon, J. R., Kutok, J. L., Le, X., Goessling, W., Neuberg, D. S., Kunkel, L. M., & Zon, L. I. (2007) · Genes & Development · doi:10.1101/gad.1545007 · Cited by 320
Self-citationTelomerase Is Required for Zebrafish Lifespan
Henriques, C. M., Carneiro, M. C., Tenente, I. M., Jacinto, A., & Ferreira, M. G. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003214 · Cited by 133
p53 ancestry: gazing through an evolutionary lens
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Premature aging in telomerase-deficient zebrafish
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Metadata
- Authors
- Berghmans, S., Murphey, R. D., Wienholds, E., Neuberg, D., Kutok, J. L., Fletcher, C. D. M., Morris, J. P., Liu, T. X., Schulte-Merker, S., Kanki, J. P., Plasterk, R., Zon, L. I., & Look, A. T.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2005-01-03
- Volume
- 102
- Issue
- 2
- Pages
- 407-412
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2064653829
- Cited by
- 597
- References
- 10
- FWCI
- 8.76
- Type
- journal article
- Language
- en
- Open access
- green
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- Berghmans, S., Murphey, R. D., Wienholds, E., Neuberg, D., Kutok, J. L., Fletcher, C. D. M., Morris, J. P., Liu, T. X., Schulte-Merker, S., Kanki, J. P., Plasterk, R., Zon, L. I., & Look, A. T. (2005). tp53 mutant zebrafish develop malignant peripheral nerve sheath tumors. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0406252102
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