Analysis Tools
homeostasis/metabolism
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• mice exposed to acid aspiration to induce acute lung injury show aggravated acute lung injury
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Allele Symbol Allele Name Allele ID |
Agtr2tm1Gsb targeted mutation 1, Gregory S Barsh MGI:1857123 |
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| Summary |
5 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exposed to acid aspiration to induce acute lung injury show aggravated acute lung injury
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• i.c.v injection of angiotensin II (100 ng) increases water intake 5-fold in adult wild-type males but has no significant effect on water intake in males homozygous for Agtr1atm1Afu and hemizygous for Agtr2tm1Gsb
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• adult males homozygous for Agtr1atm1Afu and hemizygous for Agtr2tm1Gsb show no apparent physiological changes (e.g. body weight gain) or histological abnormalities in the heart, artery or brain
• however, these mice display a higher increase in SBP after central injection of a high dose of angiotensin II (200 ng) relative to Agtr1atm1Afu homozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• on day 14 after myocardial infarction (MI), male hemizygotes exhibit a significanlty higher mortality rate (62.9%) relative to wild-type males (39.7%)
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• in male hemizygotes, VSMC-specific contractile proteins increase from birth to 8 weeks of age to a lesser extent relative to wild-type mice, suggesting impaired vascular development
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• hemizygous males exhibit delayed expression of late VSMC differentiation markers, as shown by significantly reduced protein levels of calponin and caldesmon in mutant thoracic aorta at 2 and 4 weeks after birth
• in contrast, no differences in alpha-smooth muscle actin expression (an early VSMC differentiation marker) are noted at E20, P1 or thereafter
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• at 10-12 months, mutant arteries show a significant increase in media thickness and SMC size, as shown by an ~82%, ~21% and ~26% increase of media myocyte size in femoral resistance arteries, aortas, and renal resistance arteries, respectively
• no alterations in intima, adventitia, or internal and external elastic membranes are observed
• in association with VSMC hypertrophy, mutant aortic lysates exhibit a 65% increase in P70S6 kinase phosphorylation levels relative to wild-type aortas
• treatment with an ACE inhibitor (captopril) for 8 weeks abolishes the increased pressure responsiveness, vascular hypertrophy, and enhanced P70S6 kinase phosphorylation in mutant mice
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• after MI, male hemizygotes exhibit significantly increased LV/body weight ratios (on day 14) and LV end-diastolic and end-systolic dimensions (on day 7) relative to wild-type mice, as a result of elongated myocyte length and/or increased interstitial weight
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• after MI, male hemizygotes exhibit enhanced LV dilation on days 3 and 7 as well as increased mortality in the first 2 weeks due to heart failure
• however, no differences in the rates of ventricular arrhythmia, cardiac rupture or blood pressures are observed between mutant and wild-type males after MI
• notably, interstitial fibrosis develops in the 4th week after MI and is significantly larger in mutant mice than in wild-type mice (not shown)
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• at 4 weeks, hemizygous males exhibit a significantly higher basal mean blood pressure relative to wild-type mice (105.2 4.5 vs 87.53.9 mmHg, respectively); however, no differences in blood pressure are noted at 8 weeks of age (109.2 5.7 versus 107.7 4.8 mmHg)
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• at 4 weeks, hemizygous males exhibit a significantly higher mean blood pressure than wild-type mice, when caldesmon and calponin contents are reduced in mutant mice; along with the increase in caldesmon and calponin in mutant aorta, the blood pressure difference disappears at age 8 weeks, suggesting a role in modulating smooth muscle contractility
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• at 10-12 months, male hemizygotes show no significant differences in arterial blood pressure, circulating RAS activity, heart rate, maximal LV systolic pressure or maximal LV contractility (dP/dtmax) and LV ejection fractions relative to wild-type males
• however, isolated femoral arteries from male hemizygotes display enhanced vasoconstriction to angiotensin II, norepinephrine, and K+ depolarization relative to wild-type males
• no differences in acetylcholine-induced vasorelaxation are observed, indicating unaltered endothelial function
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• hemizygous males exhibit delayed expression of late VSMC differentiation markers, as shown by significantly reduced protein levels of calponin and caldesmon in mutant thoracic aorta at 2 and 4 weeks after birth
• in contrast, no differences in alpha-smooth muscle actin expression (an early VSMC differentiation marker) are noted at E20, P1 or thereafter
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• at 10-12 months, mutant arteries show a significant increase in media thickness and SMC size, as shown by an ~82%, ~21% and ~26% increase of media myocyte size in femoral resistance arteries, aortas, and renal resistance arteries, respectively
• no alterations in intima, adventitia, or internal and external elastic membranes are observed
• in association with VSMC hypertrophy, mutant aortic lysates exhibit a 65% increase in P70S6 kinase phosphorylation levels relative to wild-type aortas
• treatment with an ACE inhibitor (captopril) for 8 weeks abolishes the increased pressure responsiveness, vascular hypertrophy, and enhanced P70S6 kinase phosphorylation in mutant mice
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• at 4 weeks, hemizygous males exhibit a significantly higher mean blood pressure than wild-type mice, when caldesmon and calponin contents are reduced in mutant mice; along with the increase in caldesmon and calponin in mutant aorta, the blood pressure difference disappears at age 8 weeks, suggesting a role in modulating smooth muscle contractility
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• at 10-12 months, male hemizygotes show no significant differences in arterial blood pressure, circulating RAS activity, heart rate, maximal LV systolic pressure or maximal LV contractility (dP/dtmax) and LV ejection fractions relative to wild-type males
• however, isolated femoral arteries from male hemizygotes display enhanced vasoconstriction to angiotensin II, norepinephrine, and K+ depolarization relative to wild-type males
• no differences in acetylcholine-induced vasorelaxation are observed, indicating unaltered endothelial function
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• after MI, male hemizygotes exhibit enhanced LV dilation on days 3 and 7 as well as increased mortality in the first 2 weeks due to heart failure
• however, no differences in the rates of ventricular arrhythmia, cardiac rupture or blood pressures are observed between mutant and wild-type males after MI
• notably, interstitial fibrosis develops in the 4th week after MI and is significantly larger in mutant mice than in wild-type mice (not shown)
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exposed to acid aspiration to induce acute lung injury show aggravated acute lung injury
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• hemizygous males develop normally and show no significant differences in daily water intake relative to wild-type males when water is freely accessible
• however, after 40 hrs of water deprivation, hemizygous males exhibit an impaired drinking response relative to wild-type males
• in addition, water-deprived hemizygous males display a significantly reduced body weight restoration relative to wild-type males at 3 hrs after water repletion
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• i.c.v injection of angiotensin II (100 ng) increases water intake 5-fold in adult wild-type males; this increase is reduced by ~40% in male hemizygotes relative to wild-type males
• in wild-type males, the effect of angiotensin II on water intake is significantly inhibited by valsartan and by PD-123319; in male hemizygotes this effect is significantly inhibited by valsartan, but not PD-123319
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• in a photobeam activity cage, hemizygous males exhibit significantly reduced locomotor activity during the dark period of the day/night cycle, particularly during the first 6 hrs (day 1); a smaller effect is noted during the dark period of the cycle on the second test day
• in contrast, no significant differences are observed during the light period of the light/dark cycle
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• hemizygous males display no differences in baseline aortic blood pressure and heart rate relative to wild-type males
• however, hemizygous males display increased vasopressor responsiveness to low-dose exogenous angiotensin II after endogenous angiotensin II production has been inhibited by captopril
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• adult hemizygous males show no significant differences in basal SBP relative to adult wild-type males (101.9 0.9 vs 98.4 0.8 mmHg, respectively)
• however, after central injection of angiotensin II, hemizygous males exhibit a significantly larger increase in SBP within the range of 50-200 ng, with no notable differences in the time course of the pressor response
• in hemizygous males, the pressor response after central injection of angiotensin II (100 ng) is inhibited ~45% by valsartan but this inhibition is significantly smaller than that in wild-type males; PD-123319 has no significant effect on SBP in mutant males
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 04/16/2024 MGI 6.23 |
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