CONDITIONAL GENE-EXPRESSION IN SECRETORY-TISSUES AND SKIN OF TRANSGENIC MICE USING THE MMTV-LTR AND THE TETRACYCLINE RESPONSIVE SYSTEM

Molecular mechanisms of development and disease can be studied in tran sgenic animals. Controlling the spatial and temporal expression patter ns of transgenes, however, is a prerequisite for the elucidation of ge ne function in the whole organism. Previously we reported that mice ca rrying a tetR/VP16 hybrid gene (tTA), under the control of the human c ytomegalovirus immediate early 1 (HCMV-IE1) gene promoter, can be used to temporally activate the expression of transgenes under the control of a promoter containing tetop sequences. We now show that the MMTV-L TR can be used to target expression of tTA to the epithelial cells of secretory organs and skin in transgenic mice. Notably, nearly uniform expression of a tetop-lacZ transgene was found in seminal vesicle, sal ivary gland, and Leydig cells of mice carrying also the MMTV-tTA trans gene. More heterogeneous patterns of gene expression were observed in mammary epithelial cells and basal cells of the epidermis. Different M MTV-tTA lines had comparable tissue expression patterns. Transcription al activation mediated by tTA was up to several hundredfold, and it wa s abrogated after the administration of tetracycline. The MMTV-tTA mic e established in this work will be useful for experiments examining th e roles of biological factors at defined developmental stages in the e pithelial cells of salivary gland, seminal vesicle, mammary gland, and skin and the Leydig cells of testes. In addition, in combination with the CRE/lox recombination system, these mice will be useful to achiev e gene deletions at defined time points in these organs. (C) 1995 Wile y-Liss, Inc.