PUBLICATION
Transgenic zebrafish line with over-expression of Hedgehog on the skin: a useful tool to screen Hedgehog-inhibiting compounds
- Authors
- Chen, Y.H., Wang, Y.H., Yu, T.H., Wu, H.J., and Pai, C.W.
- ID
- ZDB-PUB-090505-22
- Date
- 2009
- Source
- Transgenic Research 18(6): 855-864 (Journal)
- Registered Authors
- Chen, Yau-Hung
- Keywords
- Basal cell carcinoma, Keratin, Skin cancer, Sonic hedgehog, Transgenic fish, Zebrafish
- MeSH Terms
-
- Drug Evaluation, Preclinical
- Luminescent Proteins/genetics
- Zebrafish/embryology
- Zebrafish/genetics*
- Disease Models, Animal
- Animals, Genetically Modified/metabolism
- Animals
- Skin/cytology
- Skin/metabolism*
- Embryo, Nonmammalian/metabolism*
- Keratin-18/genetics
- Carcinoma, Basal Cell/drug therapy*
- Veratrum Alkaloids
- Hedgehog Proteins/antagonists & inhibitors*
- Hedgehog Proteins/genetics*
- Teratogens
- PubMed
- 19412740 Full text @ Transgenic. Res.
Citation
Chen, Y.H., Wang, Y.H., Yu, T.H., Wu, H.J., and Pai, C.W. (2009) Transgenic zebrafish line with over-expression of Hedgehog on the skin: a useful tool to screen Hedgehog-inhibiting compounds. Transgenic Research. 18(6):855-864.
Abstract
We generated a transgenic line Tg(k18:shh:RFP) with overexpression of Sonic hedgehog in the skin epidermis. By 5 day-post-fertilization (dpf), many epidermal lesions were clearly observed, including a swollen yolk sac, epidermis growth malformation around the eyes and at the basement of the pectoral fins. Skin histology revealed embryos derived from Tg(k18:shh:RFP) displayed an elevated Nuclear/Cytoplasmic ratio and pleomorphic nuclei compared to their wild type littermates, suggesting the abnormal growth pattern on the epidermis of Tg(k18:shh:RFP) embryos were dysplasia. Later (by 7 dpf), Tg(k18:shh:RFP) embryos displayed broader pectoral fins which are similar to the polydactyly phenotypes of Nevoid basal cell carcinoma syndrome (NBCCS)/Gorlin patients and polydactylous mice. In addition, treatment with cyclopamine is able to enhance and prolong the survival rates and survival durations of Tg(k18:shh:RFP) embryos. In conclusion, this unique Tg(k18:shh:RFP) fish line, should be an excellent experimental animal for screening for a lower toxicity level of the new Hh-inhibitor and can even be used as a new anti-cancer drug-screening platform.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping