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.

Medienart:

E-Artikel

Erscheinungsjahr:

2009

Erschienen:

2009

Enthalten in:

Zur Gesamtaufnahme - volume:18

Enthalten in:

Transgenic research - 18(2009), 6 vom: 28. Dez., Seite 855-64

Sprache:

Englisch

Beteiligte Personen:

Chen, Yau-Hung [VerfasserIn]
Wang, Yun-Hsin [VerfasserIn]
Yu, Tsung-Han [VerfasserIn]
Wu, Hsin-Ju [VerfasserIn]
Pai, Chiung-Wen [VerfasserIn]

Links:

Volltext

Themen:

Cyclopamine
Hedgehog Proteins
Journal Article
Keratin-18
Luminescent Proteins
Research Support, Non-U.S. Gov't
SHH protein, human
Teratogens
Veratrum Alkaloids
ZH658AJ192

Anmerkungen:

Date Completed 03.12.2009

Date Revised 20.10.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1007/s11248-009-9275-y

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM18824834X