期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1999
卷号：96
期号：15
页码：8483-8488
DOI：10.1073/pnas.96.15.8483
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Previous attempts to establish transgenic mouse models to study the functions of transforming growth factor {beta}1 (TGF{beta}1) in the skin revealed controversial roles for TGF{beta}1 in epidermal growth (inhibition vs. stimulation) and resulted in neonatal lethality in one instance. To establish a viable transgenic model for studying functions of TGF{beta}1 in the skin, we have now developed transgenic mice, which allow focal induction of the TGF{beta}1 transgene in the epidermis at different expression levels and at different developmental stages. This system, termed "gene-switch," consists of two transgenic lines. The mouse loricrin vector targets the GLVPc transactivator (a fusion molecule of the truncated progesterone receptor and the GAL4 DNA binding domain), and a thymidine kinase promoter drives the TGF{beta}1 target gene with GAL4 binding sites upstream of the promoter. These two transgenic lines were mated to generate bigenic mice, and TGF{beta}1 transgene expression was controlled by topical application of an antiprogestin. On epidermal-specific induction of the TGF{beta}1 transgene, the BrdUrd labeling index in the transgenic epidermis decreased 6-fold compared with controls. Induction of the TGF{beta}1 transgene expression also caused epidermal resistance to phorbol 12-myristate 13-acetate-induced hyperplasia, with a reduction in both epidermal thickness and BrdUrd labeling compared with those in controls. In addition, TGF{beta}1 transgene expression induced an increase in angiogenesis in the dermis. Given that the TGF{beta}1 transgene can affect both the epidermis and dermis, this transgenic model will provide a useful tool for studying roles of TGF{beta}1 in wound-healing and skin carcinogenesis in the future.
