mortality/aging
• a high proportion of double-null animals die prior to weaning
• at weaning there is a highly significant deviation of observed double homozygotes vs expected; 26 double-null pups are expected but only 7 are observed; numbers of eac genotype conform to expected ratios
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renal/urinary system
• mice have renal arterial lesions such as prominent medial hyperplasia of the interlobular arteries and afferent arterioles
(J:46007)
• at 3 weeks of age, mice demonstrate a significant increase in wall thickness vs wild-type and Agt-null mice and wall thickness ratio vs wild-type
(J:46007)
• mutants show vascular thickening compared to wild-type as measured by vascular wall thickness ratios noticeable at 1 week in renal arterioles and becoming prominent by 2 weeks (wild-type vs double-null: 0.51 vs 0.57 at 1 week, 0.51 vs 0.61 at 2 weeks and 0.55 vs 0.65 at 3 weeks)
(J:112003)
• blockade of kallikrein and bradykinin B2 receptors from 3 to 14 days accelerates vascular hypertrophy in double mutants while there is not effect in wild-type
(J:112003)
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• at 1 week of age, mice show a delay in glomerular maturity (maturity index of 1.84 in wild-type at 3 weeks of age vs 1.40 in double-nulls)
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• kidneys show progressive changes in the papilla similar to Agtr1a-null mice
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• mice have hypoplastic papilla (0.86 mm in wild-type vs 0.30 mm in mutants at 9 weeks of age)
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• kidneys show progressive changes in the calyx similar to Agtr1a-null mice
• double-null animals show a widening calyx space (calyx-to-papilla diameter ratio; ratio is 1.57 in wild-type vs 1.75 in double nulls at birth to 1.38 vs 5.65 in double nulls at 9 weeks of age
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• in all double mutants, kidneys lack the renal pelvis
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cardiovascular system
• mice have renal arterial lesions such as prominent medial hyperplasia of the interlobular arteries and afferent arterioles
(J:46007)
• at 3 weeks of age, mice demonstrate a significant increase in wall thickness vs wild-type and Agt-null mice and wall thickness ratio vs wild-type
(J:46007)
• mutants show vascular thickening compared to wild-type as measured by vascular wall thickness ratios noticeable at 1 week in renal arterioles and becoming prominent by 2 weeks (wild-type vs double-null: 0.51 vs 0.57 at 1 week, 0.51 vs 0.61 at 2 weeks and 0.55 vs 0.65 at 3 weeks)
(J:112003)
• blockade of kallikrein and bradykinin B2 receptors from 3 to 14 days accelerates vascular hypertrophy in double mutants while there is not effect in wild-type
(J:112003)
|
• 2 double-null mice that died before weaning were found to have large ventricular septal defects involving both membranous and muscular portions; none were seen in any other genotype
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• seen in 2 double-null mice that died before weaning
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• seen in 2 double-null mice that died before weaning
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• double-nulls have the lowest heart weights of any genotype but difference compared to wild-type does not reach statistical significance
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• infusion of angiotensin II cause no change in blood pressure from basline
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• in conscious animals, blood pressure averages 72 mm Hg vs 106 mm Hg in wild-type
• under anesthesia, baseline MAP is 42 mm Hg vs 96 mm Hg in wild-type controls
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