PUBLICATION
Heat shock-inducible Cre/Lox approaches to induce diverse types of tumors and hyperplasia in transgenic zebrafish
- Authors
- Le, X., Langenau, D.M., Keefe, M.D., Kutok, J.L., Neuberg, D.S., and Zon, L.I.
- ID
- ZDB-PUB-070523-29
- Date
- 2007
- Source
- Proceedings of the National Academy of Sciences of the United States of America 104(22): 9410-9415 (Journal)
- Registered Authors
- Keefe, Matthew, Langenau, David, Le, Xiuning, Zon, Leonard I.
- Keywords
- myeloproliferative disorder, RAS, rhabdomyosarcoma, intestine, malignant peripheral nerve sheath tumor
- MeSH Terms
-
- Aging/physiology
- Animals
- Animals, Genetically Modified
- Attachment Sites, Microbiological/genetics
- Gene Expression Regulation*
- Heat-Shock Response/physiology*
- Hyperplasia/genetics*
- Hyperplasia/pathology*
- Integrases/genetics
- Integrases/metabolism
- Kidney/metabolism
- Neoplasms/genetics*
- Neoplasms/pathology*
- Survival Rate
- Time Factors
- Zebrafish/genetics*
- ras Proteins/genetics
- ras Proteins/metabolism
- PubMed
- 17517602 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Le, X., Langenau, D.M., Keefe, M.D., Kutok, J.L., Neuberg, D.S., and Zon, L.I. (2007) Heat shock-inducible Cre/Lox approaches to induce diverse types of tumors and hyperplasia in transgenic zebrafish. Proceedings of the National Academy of Sciences of the United States of America. 104(22):9410-9415.
Abstract
RAS family members are among the most frequently mutated oncogenes in human cancers. Given the utility of zebrafish in both chemical and genetic screens, developing RAS-induced cancer models will make large-scale screens possible to understand further the molecular mechanisms underlying malignancy. We developed a heat shock-inducible Cre/Lox-mediated transgenic approach in which activated human kRASG12D can be conditionally induced within transgenic animals by heat shock treatment. Specifically, double transgenic fish Tg(B-actin-LoxP-EGFP-LoxP-kRASG12D; hsp70-Cre) developed four types of tumors and hyperplasia after heat shock of whole zebrafish embryos, including rhabdomyosarcoma, myeloproliferative disorder, intestinal hyperplasia, and malignant peripheral nerve sheath tumor. Using ex vivo heat shock and transplantation of whole kidney marrow cells from double transgenic animals, we were able to generate specifically kRASG12D-induced myeloproliferative disorder in recipient fish. This heat shock-inducible recombination approach allowed for the generation of multiple types of RAS-induced tumors and hyperplasia without characterizing tissue-specific promoters. Moreover, these tumors and hyperplasia closely resemble human diseases at both the morphologic and molecular levels.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping