ZFIN ID: ZDB-PUB-090505-22
Transgenic zebrafish line with over-expression of Hedgehog on the skin: a useful tool to screen Hedgehog-inhibiting compounds
Chen, Y.H., Wang, Y.H., Yu, T.H., Wu, H.J., and Pai, C.W.
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:
  • Animals
  • Animals, Genetically Modified/metabolism
  • Carcinoma, Basal Cell/drug therapy*
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Embryo, Nonmammalian/metabolism*
  • Hedgehog Proteins/antagonists & inhibitors*
  • Hedgehog Proteins/genetics*
  • Keratin-18/genetics
  • Luminescent Proteins/genetics
  • Skin/cytology
  • Skin/metabolism*
  • Teratogens
  • Veratrum Alkaloids
  • Zebrafish/embryology
  • Zebrafish/genetics*
PubMed: 19412740 Full text @ Transgenic. Res.
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.