A transgenic mouse model provides a novel biological assay of topical glucocorticosteroid potency.

Background And Design: A homozygous line of transgenic mice that expresses the human elastin promoter/CAT (chloramphenicol acetyltransferase) reporter gene construct in a tissue-specific and developmentally regulated manner is presented. Previous studies have shown that subcutaneous injections of various glucocorticosteroids up-regulate the human transgene in the mouse skin potentially through their interaction with three putative glucocorticosteroid-responsive elements contained within the human elastin promoter. In this study, we propose the use of these transgenic mice as a model system for assaying the potency of various topical glucocorticosteroid preparations.

Ultraviolet radiation activates the human elastin promoter in transgenic mice: a novel in vivo and in vitro model of cutaneous photoaging.

The major alteration in photoaged skin is the deposition of massive amounts of abnormal elastic material, termed solar elastosis. In previous work, it has been shown that solar elastosis is accompanied by increased abundance of elastin and fibrillin mRNAs and upregulation of elastin promoter activity. Using a transgenic mouse line, which expresses the human elastin promoter, linked to a chloramphenicol acetyltransferase reporter gene, in a tissue-specific and developmentally regulated manner, we investigated the effects of ultraviolet A radiation and ultraviolet B radiation on human elastin promoter activity in vivo and in vitro.

Skin elastic fibres: regulation of human elastin promoter activity in transgenic mice.

Elastic fibres form an extracellular network which provides elasticity and resilience to tissues such as the skin. To study the regulation of human elastin gene expression, we have developed a line of transgenic mice which harbour 5.2 kb of human elastin gene promoter region in their genome.

Glucocorticosteroids up-regulate human elastin gene promoter activity in transgenic mice.

Recent characterization of the human elastin gene identified three putative glucocorticoid responsive elements (GRE) within the 5'-flanking DNA. To test the functionality of these cis-elements, transgenic mice that express a human elastin promoter-reporter gene (CAT) construct in a tissue-specific manner were injected with triamcinolone acetonide (TMC) or dexamethasone (DEX), two glucocorticosteroids in clinical use. Subcutaneous injection of these glucocorticoids resulted in a marked, up to 28-fold, enhancement of the CAT activity in the skin at the site of injection.

Transforming growth factor-beta up-regulates human elastin promoter activity in transgenic mice.

We have recently developed transgenic mice which express approximately 5.2 kb of the human elastin promoter linked to the chloramphenicol acetyl transferase (CAT) reporter gene (J. Biol.