The human preprotachykinin-A gene promoter has been highly conserved and can drive human-like marker gene expression in the adult mouse CNS

Toward an understanding of the mechanisms controlling Preprotachykinin-A (P PTA) transcription, we introduced a 380-kb human yeast artificial chromosom e containing the PPTA gene tagged with the P-galactosidase gene into transg enic mice. This resulted in a pattern of LacZ expression in the central ner vous system (CNS) remarkably similar to that reported for PPTA mRNA in the rat. However, the human gene drove expression in areas of the mouse CNS not associated with strong PPTA expression in rodents but which have been show n to express PPTA in the human. This study clearly demonstrates the high de gree of conservation of the mechanisms involved in PPTA transcription that has occurred throughout 100 million of divergent human and rodent evolution . This study also defines the maximum linear extent of the human PPT-A prom oter. We believe these findings constitute the removal of a significant obs tacle in studying the transcriptional regulation of the human PPTA gene in vivo.