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Gene targeting in mice reveals a requirement for angiotensin in the development and maintenance of kidney morphology and growth factor regulation.

Publication ,  Journal Article
Niimura, F; Labosky, PA; Kakuchi, J; Okubo, S; Yoshida, H; Oikawa, T; Ichiki, T; Naftilan, AJ; Fogo, A; Inagami, T
Published in: J Clin Invest
December 1995

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.

Duke Scholars

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Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

December 1995

Volume

96

Issue

6

Start / End Page

2947 / 2954

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta
  • Restriction Mapping
  • RNA, Messenger
  • Platelet-Derived Growth Factor
  • Organ Size
  • Mice, Mutant Strains
  • Mice, Knockout
  • Mice
  • Kidney Medulla
  • Kidney Glomerulus
 

Citation

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Niimura, F., Labosky, P. A., Kakuchi, J., Okubo, S., Yoshida, H., Oikawa, T., … Inagami, T. (1995). Gene targeting in mice reveals a requirement for angiotensin in the development and maintenance of kidney morphology and growth factor regulation. J Clin Invest, 96(6), 2947–2954. https://doi.org/10.1172/JCI118366
Niimura, F., P. A. Labosky, J. Kakuchi, S. Okubo, H. Yoshida, T. Oikawa, T. Ichiki, A. J. Naftilan, A. Fogo, and T. Inagami. “Gene targeting in mice reveals a requirement for angiotensin in the development and maintenance of kidney morphology and growth factor regulation.J Clin Invest 96, no. 6 (December 1995): 2947–54. https://doi.org/10.1172/JCI118366.
Niimura F, Labosky PA, Kakuchi J, Okubo S, Yoshida H, Oikawa T, et al. Gene targeting in mice reveals a requirement for angiotensin in the development and maintenance of kidney morphology and growth factor regulation. J Clin Invest. 1995 Dec;96(6):2947–54.
Niimura, F., et al. “Gene targeting in mice reveals a requirement for angiotensin in the development and maintenance of kidney morphology and growth factor regulation.J Clin Invest, vol. 96, no. 6, Dec. 1995, pp. 2947–54. Pubmed, doi:10.1172/JCI118366.
Niimura F, Labosky PA, Kakuchi J, Okubo S, Yoshida H, Oikawa T, Ichiki T, Naftilan AJ, Fogo A, Inagami T. Gene targeting in mice reveals a requirement for angiotensin in the development and maintenance of kidney morphology and growth factor regulation. J Clin Invest. 1995 Dec;96(6):2947–2954.

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

December 1995

Volume

96

Issue

6

Start / End Page

2947 / 2954

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta
  • Restriction Mapping
  • RNA, Messenger
  • Platelet-Derived Growth Factor
  • Organ Size
  • Mice, Mutant Strains
  • Mice, Knockout
  • Mice
  • Kidney Medulla
  • Kidney Glomerulus