Analysis Tools
mortality/aging
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• mice start dying at 4 weeks after tamoxifen (TMX) administration; the median survival age is 6 weeks and no mice survive for >8 weeks
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growth/size/body
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• at 4 weeks after TMX treatment, mice exhibit significantly enlarged hearts relative to controls
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cardiovascular system
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• at 2 weeks after TMX treatment, LV myocardium exhibits sarcomeric disarray and swollen mitochondria, unlike in control hearts
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• at 2 weeks after TMX treatment, cross-sectional area of cardiomyocytes is reduced relative to that in control mice
• adult cardiomyocytes isolated from TMX-treated mice are significantly thinner and shorter than those of control mice
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• atrial chambers are enlarged at 4 weeks after TMX treatment
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• interventricular septum is thinner than normal at 4 weeks after TMX treatment
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• at 4 weeks after TMX treatment, mice exhibit significantly enlarged hearts relative to controls
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• left ventricle (LV) wall is thinner than normal at 4 weeks after TMX treatment
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• ventricular chambers are enlarged at 4 weeks after TMX treatment
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• at 4 weeks after TMX treatment, mice show increased interstitial fibrosis in the LV and interventricular septum relative to controls
• the cardiac fibrotic index is already increased at 1 week after TMX treatment and becomes significantly increased thereafter
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• TMX-treated mice develop lethal dilated cardiomyopathy
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• TMX-treated mice show markedly lower basal inotropy and lusitropy and only very weak reactivity to stimulation with increasing units of dobutamine
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• at 4 weeks after TMX treatment, LV fractional shortening percentage (LVFS %) is significantly reduced relative to that in controls
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• in culture, adult ventricular myocytes isolated from TMX-treated mice show significantly reduced protein synthesis relative to controls, as assessed by a [3H]leucine uptake assay
• TMX-treated mice show a progressive (2- to 8-fold) increase in the expression of cardiac fetal genes (Nppa, Myh7, Acta1) relative to controls at 2 weeks and 4 weeks post-TMX
• TMX-treated mice show a progressive reduction in cytochrome c oxidase subunit IV (CoxIV) expression, indicating a loss in the oxidative capacity of myocardial mitochondria
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• TMX-treated mice show a progressive and severe loss of cardiomyocytes due to apoptosis, as shown by TUNEL staining
• at 4 weeks after TMX treatment, cleaved Parp expression is significantly increased in the heart relative to that in control mice
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• at 2 weeks after transverse aortic constriction (TAC), i.e. 3 weeks post-TMX treatment, mice show an impaired hypertrophic response and accelerated heart failure progression, as determined by a significantly reduced increase in LV wall thickness, a more dilated LV chamber, a significantly reduced ratio of LV weight- and heart weight-to-tibial length, accelerated contractile dysfunction, reduced induction of cardiac fetal genes, and significantly reduced survival relative to control TAC mice, with a 40% death rate already noted after 1 week of TAC
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• at 4 weeks after TMX treatment, mice exhibit heart failure, as assessed by echocardiography and the dobutamine stress test
• however, cardiac function is maintained up to 2-3 weeks after TMX treatment
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cellular
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• at 4 weeks after TMX treatment, mice show increased interstitial fibrosis in the LV and interventricular septum relative to controls
• the cardiac fibrotic index is already increased at 1 week after TMX treatment and becomes significantly increased thereafter
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• TMX-treated mice show a progressive and severe loss of cardiomyocytes due to apoptosis, as shown by TUNEL staining
• at 4 weeks after TMX treatment, cleaved Parp expression is significantly increased in the heart relative to that in control mice
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• at 2 weeks after TMX treatment, LV myocardium exhibits swollen mitochondria, unlike in control hearts
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• at 1 week after TMX treatment, cardiac expression of several autophagy-related proteins is increased and autophagic bodies are observed in the myocardium, unlike in control hearts
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• TMX-treated mice show a progressive reduction in cytochrome c oxidase subunit IV (CoxIV) expression, indicating reduced oxidative capacity of myocardial mitochondria
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• in culture, adult ventricular myocytes isolated from TMX-treated mice show significantly reduced protein synthesis relative to controls, as assessed by a [3H]leucine uptake assay
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homeostasis/metabolism
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• at 2 weeks after transverse aortic constriction (TAC), i.e. 3 weeks post-TMX treatment, mice show an impaired hypertrophic response and accelerated heart failure progression, as determined by a significantly reduced increase in LV wall thickness, a more dilated LV chamber, a significantly reduced ratio of LV weight- and heart weight-to-tibial length, accelerated contractile dysfunction, reduced induction of cardiac fetal genes, and significantly reduced survival relative to control TAC mice, with a 40% death rate already noted after 1 week of TAC
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• at 1 week after TMX treatment, cardiac expression of several autophagy-related proteins is increased and autophagic bodies are observed in the myocardium, unlike in control hearts
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• in culture, adult ventricular myocytes isolated from TMX-treated mice show significantly reduced protein synthesis relative to controls, as assessed by a [3H]leucine uptake assay
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• TMX-treated mice exhibit pleural effusions
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muscle
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• at 2 weeks after TMX treatment, LV myocardium exhibits sarcomeric disarray and swollen mitochondria, unlike in control hearts
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• at 2 weeks after TMX treatment, cross-sectional area of cardiomyocytes is reduced relative to that in control mice
• adult cardiomyocytes isolated from TMX-treated mice are significantly thinner and shorter than those of control mice
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• TMX-treated mice develop lethal dilated cardiomyopathy
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• TMX-treated mice show markedly lower basal inotropy and lusitropy and only very weak reactivity to stimulation with increasing units of dobutamine
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• at 4 weeks after TMX treatment, LV fractional shortening percentage (LVFS %) is significantly reduced relative to that in controls
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• TMX-treated mice show a progressive and severe loss of cardiomyocytes due to apoptosis, as shown by TUNEL staining
• at 4 weeks after TMX treatment, cleaved Parp expression is significantly increased in the heart relative to that in control mice
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• at 2 weeks after TMX treatment, LV myocardium exhibits sarcomeric disarray, unlike in control hearts
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respiratory system
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• TMX-treated mice exhibit pleural effusions
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