SPECIFIC EXPRESSION IN MOUSE MESODERM-DERIVED AND NEURAL CREST-DERIVED TISSUES OF A HUMAN PDGFRA PROMOTER LACZ TRANSGENE/

The platelet-derived growth factor a-receptor (PDGFR-alpha) displays a Lineage-specific expression pattern in the mouse embryo and is requir ed for normal development of mesoderm and cephalic neural crest deriva tives. The purpose of the present study was to demonstrate the in vivo promoter function of genomic DNA fragments representing the 5'-flanki ng part of the human PDGFRA gene. 2.2, 0.9 and 0.4 kb PDGFRA promoter fragments, ligated to a lacZ reporter gene, were microinjected into fe rtilized mouse eggs and transgenic mouse lines were established. The e xpression patterns were basically similar in the 2.2 and 0.9 kb lines and overlapped grossly the endogenous Pdgfra gene expression pattern. The transgenic line with the highest expression level was chosen for d etailed analysis. Expression was, as expected, mainly confined to tiss ues of mesodermal and neural crest origin. No expression was found in epithelial tissues of endo-or ectodermal origin. The promoter fragment s were also active in neuroepithelium and in certain neuronal cell typ es that did not faithfully express PDGFR-alpha mRNA, while they failed to specify reporter expression in PDGFR-alpha expressing O-2A progeni tor cells and other glial elements of the central nervous system. Thus , the isolated human PDGFRA promoter contains most but not all of the regulatory elements that are necessary to establish tissue specific ge ne expression during development. (C) 1998 Elsevier Science Ireland Lt d.