Transgenic mice studies of immediate-early genes: from markers to mutants

Abstract

Eurokaryotic cells can selectively modify gene transcription in response to alterations in the levels of extracellular signals. In general, genomic targets of extracellular stimuli can be devided into two categories based upon the characteristics of their regulation (reviewed in Curran and Morgan 1987; Morgan and Curran 1989). Thus, alterations in transcription of “primary response” genes is independent of protein synthesis and is typically initiated within minutes. In contrast, changes in the expression of “delayed”, or “late response” genes occur with a lag of several hours and requires ongoing protein synthesis. This nomenclature is based partly upon analogies with certain viruses that control their replicative cycle by the sequential activation of groups of genes (i.e. immediate-early, early and late genes). As their name suggests, viral immediate-early genes are transcriptionally active immediately upon infection of the host cell and are transcribed even in the absence of protein synthesis. Their products serve to coordinate further progression of the viral life cycle by regulating transcription of viral early genes (reviewed in Berk 1986). This has led, again by analogy, to the suggestion that the proteins encoded by the cellular primary response genes contribute to the transcriptional regulation of late response genes (Goelet et al. 1986; Morgan and Curran 1989). This would also imply that primary response gene products should encode inducible transcription factors or proteins capable of modifying the activity of existing transcription factors.