Gene targeting in mice reveals a requirement for angiotensin in the development and maintenance of kidney morphology and growth factor regulation.
Journal Article (Journal Article)
Elevated levels of endogenous angiotensin can cause hypertensive nephrosclerosis as a result of the potent vasopressor action of the peptide. We have produced by gene targeting mice homozygous for a null mutation in the angiotensinogen gene (Atg-1-). Postnatally, Atg-1- animals show a modest delay in glomerular maturation. Although Atg-1- animals are hypotensive by 7 wk of age, they develop, by 3 wk of age, pronounced lesions in the renal cortex, similar to those of hypertensive nephrosclerosis. In addition, the papillae of homozygous mutant kidneys are reduced in size. These lesions are accompanied by local up-regulation of PDGF-B and TGF-beta1 mRNA in the cortex and down-regulation of PDGF-A mRNA in the papilla. The study demonstrates an important requirement for angiotensin in achieving and maintaining the normal morphology of the kidney. The mechanism through which angiotensin maintains the volume homeostasis in mammals includes promotion of the maturational growth of the papilla.
Full Text
Duke Authors
Cited Authors
- Niimura, F; Labosky, PA; Kakuchi, J; Okubo, S; Yoshida, H; Oikawa, T; Ichiki, T; Naftilan, AJ; Fogo, A; Inagami, T
Published Date
- December 1995
Published In
Volume / Issue
- 96 / 6
Start / End Page
- 2947 - 2954
PubMed ID
- 8675666
Pubmed Central ID
- PMC186006
International Standard Serial Number (ISSN)
- 0021-9738
Digital Object Identifier (DOI)
- 10.1172/JCI118366
Language
- eng
Conference Location
- United States