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 (PPTA) transcription, we introduced a 380-kb human yeast artificial chromosome containing the PPTA gene tagged with the beta-galactosidase gene into transgenic mice. This resulted in a pattern of LacZ expression in the central nervous 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 shown to express PPTA in the human. This study clearly demonstrates the high degree 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 promoter. We believe these findings constitute the removal of a significant obstacle in studying the transcriptional regulation of the human PPTA gene in vivo.
MacKenzie
A
A
Department of Veterinary Pathology, Royal (Dick) School of Veterinary Studies, Summerhall Square, The University of Edinburgh, Edinburgh EH91QH, Scotland.
Payne
C
C
Boyle
S
S
Clarke
A R
AR
Quinn
J P
JP
D000367:Age Factors; D000818:Animals; D015415:Biomarkers; D002490:Central Nervous System / Q000737:chemistry* / Q000502:physiology*; D003001:Cloning, Molecular; D017124:Conserved Sequence; D019143:Evolution, Molecular; D005260:Female; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D007763:Lac Operon; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics*; D051381:Rats; D015320:Tachykinins / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics
D015415:Biomarkers; D011498:Protein Precursors; D015320:Tachykinins; C044206:preprotachykinin