Transgenic zebrafish line with over-expression of Hedgehog on the skin: a useful tool to screen Hedgehog-inhibiting compounds.
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.
Chen
Yau-Hung
YH
Graduate Institute of Life Sciences, Tamkang University, No. 151 Ying-chuan Road, Tamsui, Taipei County, 251, Taiwan. yauhung@mail.tku.edu.tw
Wang
Yun-Hsin
YH
Yu
Tsung-Han
TH
Wu
Hsin-Ju
HJ
Pai
Chiung-Wen
CW
D000818:Animals; D030801:Animals, Genetically Modified / Q000378:metabolism; D002280:Basal Cell Carcinoma / Q000188:drug therapy*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004625:Embryo, Nonmammalian / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics*; D053538:Keratin-18 / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D013723:Teratogens; D014704:Veratrum Alkaloids; D015027:Zebrafish / Q000196:embryology / Q000235:genetics*
D053823:Hedgehog Proteins; D053538:Keratin-18; D008164:Luminescent Proteins; C509239:SHH protein, human; D013723:Teratogens; D014704:Veratrum Alkaloids; C000541:cyclopamine