Partial Tissue-Specific Expression of Two Human Angiotensinogen Promoter-Lacz Transgenes in Mice

Abstract

P13 Previous analysis of transgenic mice carrying a genomic construct encoding the human angiotensinogen (HAGT) gene indicated that the 13.7 Kb sequence harbored all cis elements required for the appropriate tissue and cell expression of HAGT in vivo . In addition, analysis of independently derived HAGT transgenic lines suggested the presence of a locus control element (LCR) in the HAGT gene since the expression levels were proportional to transgene copy number. In attempt to identify cis elements responsible for the regulation of HAGT expression in vivo we created several new transgenic mouse lines carrying either 1.5 Kb of the HAGT promoter or 1.5 kb of the promoter along with the first exon and intron of the HAGT gene fused to the LacZ reporter gene. Reporter gene expression did not correlate with transgene copy number suggesting the absence of a putative LCR element in the 1.5 Kb region proximal to the HAGT transcription start site. LacZ expression was most prominent in liver and adrenal gland, with additional expression in heart, testis, brain, and cerebellum. Most other tissues (including kidney) had little to no expression of the reporter gene. Our results indicate that the regions proximal to the HAGT transcription start site contain cis -acting elements important for appropriate HAGT expression in the liver and some, but not all, extra-hepatic tissues which should express HAGT. Further dissection of the genomic HAGT sequence will be required to identify all elements involved in proper in vivo regulation of the HAGT gene.