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| Chimeric mice carrying 'regional' targeted deletion of the angiotensin type 1A receptor gene - Evidence against the role for local angiotensin in the in vivo feedback regulation of renin synthesis in juxtaglomerular cells |
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| Author(s): Matsusaka T, Nishimura H, Utsunomiya H, Kakuchi J, Niimura F, Inagami T, Fogo A, Ichikawa I |
| Source: JOURNAL OF CLINICAL INVESTIGATION Volume: 98 Issue: 8 Pages: 1867-1877 Published: OCT 15 1996 |
| Times Cited: 77 References: 17 |
| Abstract: We have developed chimeric mice carrying 'regional' null mutation of the angiotensin type 1A (AT1A) receptor, the AT1 receptor subtype exclusively present in mouse juxtaglomerular (JG) cells. The chimeric mouse (Agtr1a -/- <-> +/+) is made up of wild-type (Agtr1a +/+) cells or cells homozygous for Agtr1a deletion (Agtr1a -/-). In the latter, the AT1A coding exon was replaced with a reporter gene, lacZ. In Agtr1a -/- <-> +/+ mice, these two clones of cells are found to be clustered and display patchy distributions in the kidney and heart. Tracking of lacZ activities in hetero(Agtr1a +/-) and homozygous (Agtr1a -/-) deletion mutant offspring from Agtr1a -/- <-> +/+ mice revealed that the promoter activity of Agtr1a is localized in JG cells, afferent arteriolar walls, glomerular mesangial region and endothelial cells, and apical and basolateral proximal tubule membranes. The JG apparatuses of Agtr1a -/- mice are markedly enlarged with intense expression of renin mRNA and protein. In Agtr1a -/- <-> +/+ mice, these changes were proportional to the degree of chimerism. Within a given Agtr1a -/- <-> +/+ mouse, however, the degree of JG hypertrophy/hyperplasia and the expression of renin mRNA and protein were identical between Agh-la +/+ and Agtr1a -/- cells. Thus, in the in vivo condition tested, the local interaction between angiotensin and the AT1 receptor on the JG cells has little functional contribution to the feedback regulation of JG renin synthesis. |
| Document Type: Article |
| Language: English |
| Reprint Address: Matsusaka, T (reprint author), VANDERBILT UNIV, MED CTR, DEPT PEDIAT, DIV NEPHROL, SCH MED, MCN C4204, NASHVILLE, TN 37232 USA |
Addresses:
1. VANDERBILT UNIV, SCH MED, DEPT BIOCHEM, NASHVILLE, TN 37232 USA
2. VANDERBILT UNIV, SCH MED, DEPT PATHOL, NASHVILLE, TN 37232 USA |
| Publisher: ROCKEFELLER UNIV PRESS, 222 E 70TH STREET, NEW YORK, NY 10021 |
| Subject Category: Medicine, Research & Experimental |
| IDS Number: VN973 |
| ISSN: 0021-9738 |
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