Key result
Mice homozygous for a null mutation in the angiotensinogen gene showed delayed glomerular maturation and developed pronounced renal cortical lesions by 3 weeks of age.
Why the study?
Does targeted disruption of the angiotensinogen gene affect kidney morphology and growth factor regulation in mice?
Does targeted disruption of the angiotensinogen gene affect kidney morphology and growth factor regulation in mice?
Absolute Event Rate: 1.88% vs 2.41%
p-value: p=<0.05
Targeted disruption of the angiotensinogen gene in mice demonstrates an essential requirement for angiotensin in maintaining normal postnatal kidney morphology and volume homeostasis.
Angiotensin required for murine kidney maturation; leaves open relevance to human RAS inhibitor effects or congenital disease.
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.
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Niimura et al. (1995) studied Angiotensinogen deficiency (n=148). Angiotensinogen gene knockout (Atg-/-) vs. Wild-type (Atg+/+) was evaluated on Glomerular maturity index in inner cortex at 1 week (p=<0.05). Mice homozygous for a null mutation in the angiotensinogen gene showed delayed glomerular maturation and developed pronounced renal cortical lesions by 3 weeks of age.
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