Phenotypic characterization of transgenic mice with "knockout" for the angiotensin converting enzyme

Academic Article

Abstract

  • Krege and associates have generated a strain of mice that carries an insertional mutation that inactivates angiotensin converting enzyme (ACE). The current study characterized the phenotype of these mice by measuring ACE activity, ACE mRNA levels, baseline blood pressure (BP) and BP responses to exogenous angiotensin I (AI) and II (AII) and bradykinin (BK). BP was measured in conscious unrestrained mice at age 10 to 12 wks via a carotid cannula. ACE activity was quantitated by a novel method combining HPLC with spectrophotometric assay of hippuric acid generated by incubating samples with the artificial substrate, hippuryl histidyl leucine. ACE mRNA was quanttated by Northern analysis and standardized with 18S rRNA. Offspring of mating wildtype males (two copies of ACE gene, 1/1) with heterozygote females (one copy, 1/0) were studied. Results (mean±SEM; n): Genotype B.W. Baseline BP ΔBP post All ΔBP post Al ΔBP post BK (gm) (mmHg) (mmHg) (mmHg) (mmHg) 1/1 25±1(19) 105±4(19) 32±2(12) 30±2(7) -14±3(6) 1/0 27±1(16) 109±2(16) 30±2(10) 23±2 (6) * -32±3*(7) ACE mRNA/18S rRNA ratios (n=5) ACE activity (mU/ml/hr, n=5) Heart Lung Kidney Plasma Heart Lung 1/1 100±13 889±43 462±43 15±3 34±4 1080±90 1/0 62±3 * 363±94 * 277±39 * 6.6±1 * 9±1 * 310±20 * * p< 0.05, compared to respective values of 1/1. These data indicate that mice expressing a single copy of the ACE gene have decreased tissue ACE mRNA levels and ACE activity and reduced ability to convert exogenous Al to All and to hydrolyze exogenous BK. Nevertheless, these mice maintain normal resting BP and pressor responses to All. These mice provide an useful model to study the effects of reduced ACE gene expression on cardiovascular function and structure under resting and stressed conditions.
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    Author List

  • Tian B; Meng QC; Chen YF; Krege JH; Oparil S
  • Volume

  • 44
  • Issue

  • 1