TRANSACTIVATION OF HOX GENE-EXPRESSION IN A VP16-DEPENDENT BINARY TRANSGENIC MOUSE SYSTEM

Mice with aberrant expression of Hox genes have provided valuable insi ght into the role of Hox class transcription factors in patterning the developing skeleton and the nervous system. However, a recurrent prob lem is the lethality of mice expressing a Hox-transgene. To circumvent premature death frequently associated with transgenes that interfere with development, we have established a binary transgenic mouse system . Transactivator mice harbor the VP16 gene regulated by a promoter of interest while transresponder mice contain the VP16-responsive immedia te early (IE) promoter linked to the gene to be expressed [G.W. Byrne, F.H. Ruddle, Multiplex gene regulation: a two-tiered approach to tran sgene regulation in transgenic mice, Proc. Natl. Acad. Sci. U.S.A., 86 (1989) 5473-5477]. Here, we report the generation of transresponder m ouse strains that harbor murine homeobox genes linked to the IE promot er. We provide evidence that these transgenes are transcriptionally ac tivated in progeny that inherit both a transactivator and transrespond er transgene. By microdissection of mouse embryos and reverse transcri ption polymerase chain reaction (RT-PCR) analysis, we demonstrate that the expression of the Hox-transgenes is restricted to those regions o f the mouse embryos where VP16 is present. The ability to activate sta ble Hox-transgenes in a reproducible fashion now permits a detailed in vivo dissection of the molecular mechanisms that lead to developmenta l abnormalities caused by deregulated Hox-gene expression, (C) 1998 El sevier Science B.V. All rights reserved.