The angiotensinogen gene is expressed in both astrocytes and neurons in murine central nervous system

Two transgenic mouse models were used to examine the cellular localization of angiotensinogen (AGT) in the brain. The first model was previously descr ibed in detail and consists of a human AGT genomic transgene containing all exons and introns of the gene and 1.2 kb of the 5' flanking DNA. The secon d model contains a fusion between 1.2 kb of HAGT 5' flanking DNA and the be ta-gal reporter gene which exhibits a similar pattern of tissue-specific ex pression to the HAGT transgene. Expression of both transgenes qualitatively mirrors the expression of endogenous AGT. Double staining of transgenic mo use brain sections with X-gal and GFAP revealed that a majority of beta-gal activity was localized to astrocytes in almost all brain areas. However, b oth P-gal activity as identified by X-gal, and HAGT mRNA as detected by in situ hybridization, were also found in neurons in restricted areas of the b rain, including the mesencephalic trigeminal nucleus (meV), subfornical org an (SFO) and the external lateral parabrachial nucleus (elPB). The expressi on of these transgenes provides the first convincing evidence for AGT gene expression in neurons in the brain. We further report by angiotensin II (An g-II) immunostaining in rat brains after selective lesioning, that Ang-II i s likely involved in a neuronal pathway from the PB to the amygdala (Ce), F inally, we performed double-labeling, first by retrograde labeling of HRP i njected into the Ce, and then by X-gal on PB neurons in beta-gal transgenic mice, and identified doubly labeled neurons. Based on these results, we pr opose that AGT is generated in neurons in the elPB, transported to the Ce a nd converted into Ang-II locally to exert is biological functions. (C) 1999 Elsevier Science B.V. All rights reserved.