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See article by Gao et al. [1] (pages 197–204) in this issue. Manipulation of the mouse genome by transgenic approaches is a powerful tool to examine gene function as well as interaction of gene products in the intact animal [2–4]. In the past, gain-in-function models were the most frequently used transgenic animals to define the physiological relevance of gene products. In these animals, transgene expression is controlled by well characterized promoter elements that drive transgene expression by their cardio-specificity, while the onset of transgene expression depends on the temporal activation of the promotor employed [5–11]. However, the temporal regulation of transgene expression might prevent investigation of a number of important questions. In its worst case, the inappropriate onset of transgene expression can interfere with proper embryonal development resulting in early lethal phenotypes [12–14]. Less dramatically but more commonly, constitutive transcriptional activity of the promoter does not provide any information on developmental aspects of transgene expression [15–17] and prevents examination of the gene dosis and phenotype [18,19]. These limitations are overcome by conditional transgenic systems allowing control of the timing as well as the spatial pattern of gene expression (for reviews, see Refs. [20,21]).To date a number of conditional gene expression systems have been introduced [22–26]. Among them the tetracycline-regulated binary system based on the tetracycline (tet) resistance operon of E. coli has emerged as the present system … * Corresponding author. Tel.: +49-622-156-8670; fax: +49-622-156-5516. hugo_katus{at}med.uni-heidelberg.de

Conditional AC type VI expression in the heart: relevant insights into function of inducible target gene expression