IMPLEMENTING TRANSGENIC AND EMBRYONIC STEM-CELL TECHNOLOGY TO STUDY GENE-EXPRESSION, CELL-CELL INTERACTIONS AND GENE-FUNCTION

This review highlights the use of transgenic mice and gene targeting i n the study of reproduction, pituitary gene expression, and cell linea ge. Since 1980 numerous applications of transgenic animal technology h ave been reported. Altered phenotypes resulting from transgene express ion demonstrated that introduced genes can exert profound effects on a nimal physiology. Transgenic mice have been important for the study of hormonal and developmental control of gene expression because gene ex pression in whole animals often requires more DNA sequence information than is necessary for expression in cell cultures. This point is illu strated by studies of pituitary glycoprotein hormone alpha- and beta-s ubunit gene expression (Kendall et al., Mol Endocrinol 1994; in press [1]. Transgenic mice have also been invaluable for producing animal mo dels of cancer and other diseases and testing the efficacy of gene the rapy. In addition, cell-cell interactions and cell lineage relationshi ps have been explored by cell-specific expression of toxin genes in tr ansgenic mice. Recent studies suggest that attenuated and inducible to xins hold promise for future transgene ablation experiments. Since 198 7, embryonic stem (ES) cell technology has been used to create numerou s mouse strains with targeted gene alterations, contributing enormousl y to our understanding of the functional importance of individual gene s. For example, the unexpected development of gonadal tumors in mice w ith a targeted disruption of the inhibin gene revealed a potential rol e for inhibin as a tumor suppressor (Matzuk et al., Nature 1992:360: 3 13-319 [2]. The transgenic and ES cell technologies will undoubtedly c ontinue to expand our understanding and challenge our paradigms in rep roductive biology.