Analysis Tools|
Allele Symbol Allele Name Allele ID |
Nkx2-5tm2(cre)Rph targeted mutation 2, Richard P Harvey MGI:2448972 |
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| Summary |
16 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• embryos are present at Mendelian ratios up to E13.5, but fail to survive past E13.7; only 10% are recovered at E13.7-E14.0 and those found alive are close to expiration
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• a thin, improperly compacted ventricular myocardium is observed at E13.0
• however, no significant increase in cell death is noted in the abnormal myocardium
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• mRNA levels of Pitx2 (critical in the establishment of OFT positioning relative to the ventricles) are upregulated in the OFT and adjacent ventricular wall starting from E10.25 and as late as E13.0
• mRNA expression of Sema3c is upregulated in the OFT and adjacent ventricular wall starting at E12.5
• mesenchymal apoptosis is significantly reduced in the OFT at E13.0 and E13.5, but not at E12.5 or earlier; a ~5-fold decrease in mesenchymal cell death is noted in the OFT at E12.75-E13.0
• however, no change in cell proliferation is detected at E12.0, E12.5 or E13.0
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• by E13.0-E13.5, fifteen of 19 (79%) of hearts exhibit DORV with a concurrent ventricular septal defect (VSD)
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• by E13.0-E13.5, fifteen of 19 (79%) of hearts exhibit DORV with a concurrent VSD
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• a thin, improperly compacted ventricular myocardium is observed at E13.0
• however, no significant increase in cell death is noted in the abnormal myocardium
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at E9.5, atrioventricular (AV) cushions exhibit significantly lower numbers of mesenchymal cells than control AV cushions, suggesting disruption of endothelial to mesenchymal transition (EndMT)
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• hypoplastic and fragmented
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• hypoplastic and fragmented
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• hypoplastic and fragmented
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• significant decrease of mitotic mesenchymal cells in the anlagen
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• hypoplastic and fragmented
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• significant decrease of mitotic mesenchymal cells in the anlagen
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• partial rescue of spleen expansion compared to mutant mice wild-type for Cdkn2b and spleens form a single compact anlage
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• significant rescue of mesenchymal proliferation compared to mutant mice wild-type for Cdkn2b
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• partial rescue of spleen expansion compared to mutant mice wild-type for Cdkn2b and spleens form a single compact anlage
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• significant rescue of mesenchymal proliferation compared to mutant mice wild-type for Cdkn2b
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• hypoplastic and fragmented
• more severe than in mutant mice wild-type for Pbx2
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• hypoplastic and fragmented
• more severe than in mutant mice wild-type for Pbx2
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• most die between E10.5 and E12.5 with few surviving to die by E14.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• most die between E10.5 and E12.5 with few surviving to die by E14.5
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• at E13.5, glycogen storage in embryonic hearts is decreased compared to in wild-type mice
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• at E13.5, the degree of cardiomyocyte differentiation towards the ventricular lumen is lower than in wild-type mice
• at E13.5, cardiomyocytes have less mature sarcomeres with shorter, randomly arranged muscle fibrils unlike in wild-type mice
• however, mice exhibit normal cardiac morphology at E10.5 and E12.5
• at E13.5, cardiomyocytes accumulate a fine granular material unlike in wild-type cells
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• at E13.5, a subset of cardiomyocytes contain irregular mitochondria
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• at E11.5, proliferation of cardiomyocytes is decreased 45% compared to in wild-type mice
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• at E13.5, a subset of cardiomyocytes contain irregular mitochondria
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• at E11.5, proliferation of cardiomyocytes is decreased 45% compared to in wild-type mice
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• at E12.5 and E14.5, respiratory chain complex III activity in cardiomyocytes is 10% of normal
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• at E13.5, glycogen storage in embryonic hearts is decreased compared to in wild-type mice
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• at E13.5, glycogen storage in embryonic hearts is decreased compared to in wild-type mice
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• at E13.5, a subset of cardiomyocytes contain irregular mitochondria
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• at E11.5, proliferation of cardiomyocytes is decreased 45% compared to in wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 13% of mice die between 9 and 15 months of age with varying degrees of dilated cardiomyopathy
• however, mice exhibit no embryonic lethality
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• at 8 weeks, pale and granulated cells resembling degenerating cardiomyocytes are found in the ventricular myocardium unlike in wild-type mice
• at 1 year, severely affected mice exhibit hypertrophic cardiocyocytes
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• at E13.5, a subset of cardiomyocytes contain irregular mitochondria
• however, no other cardiac abnormalities are observed at E13.5
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• in severely affected mice at 1 year
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• in severely affected mice at 1 year
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• in severely affected mice at 1 year
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• in mice with hypertrophic cardiomyocytes at 1 year
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• in severely affected mice at 1 year
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• at 1 year, mice with dilated cardiomyopathy exhibit increased interstitial fibrosis compared to mice that develop a hypertrophic cardiomyocyte-like phenotype
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• in severely affected mice at 1 year
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• at 1 year, 40% of mice exhibit pathologies of the cardiac conduction system including first degree atrioventricular (AV) block or intermittent second degree AV block type II
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• at 1 year, 40% of mice exhibit pathologies of the cardiac conduction system including sinus bradycardia
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• at 1 year, 40% of mice exhibit pathologies of the cardiac conduction system including transient bundle branch block
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• respiratory chain complex III activity in cardiomyocytes is reduced 43% at E12.5 and 56% at E14.5 compared to in wild-type cells
• however, cardiomyocytes is reduced at 8 weeks is normal
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• at E13.5, a subset of cardiomyocytes contain irregular mitochondria
• however, no other cardiac abnormalities are observed at E13.5
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• at 1 year, mice with dilated cardiomyopathy exhibit increased interstitial fibrosis compared to mice that develop a hypertrophic cardiomyocyte-like phenotype
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• respiratory chain complex III activity in cardiomyocytes is reduced 43% at E12.5 and 56% at E14.5 compared to in wild-type cells
• however, cardiomyocytes is reduced at 8 weeks is normal
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• in severely affected mice at 1 year
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• at 8 weeks, pale and granulated cells resembling degenerating cardiomyocytes are found in the ventricular myocardium unlike in wild-type mice
• at 1 year, severely affected mice exhibit hypertrophic cardiocyocytes
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• at E13.5, a subset of cardiomyocytes contain irregular mitochondria
• however, no other cardiac abnormalities are observed at E13.5
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• in severely affected mice at 1 year
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• in severely affected mice at 1 year
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• increase in heart to body weight ratio
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• increase in heart to body weight ratio
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at E12.5, the relative volume of abnormal heart tissue begins to decline to 42% in ventricles and 47% in atria and is further reduced at E16.5 to 18% in ventricles and 19% in the atria then 10% in ventricles and 17% in the atria prior to birth
• at E12.5 and E13.5, cardiomyocytes appear small and round compared to wild-type cells
• however, the absolute volume of heart tissue before birth is unchanged
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• cardiomyocytes appear smaller at E12.5 and E13.5
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• while the number of affected cardiomyocytes decreases proliferation of normal cardiomyocytes increases in a compensatory manner
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• while the number of affected cardiomyocytes decreases proliferation of normal cardiomyocytes increases in a compensatory manner
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• while the number of affected cardiomyocytes decreases proliferation of normal cardiomyocytes increases in a compensatory manner
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no abnormalities are detected in cardiomyocyte proliferation during cardiogenesis
• no abnormalities detected in adult cardiac function or morphology
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• delay in septation indicated by absence of cushion of the atrioventricular cushions at E12.5
• however, by E16.5 septation is complete
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• at E12.5 in the left ventricle
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• significantly smaller at E9.5, E12.5, and E16.5
• however, by P0 and P7 heart size is similar to wild-type controls
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• significantly thinner at E9.5, E12.5, and E16.5
• however, by P7 wall thickness is similar to wild-type controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• conditional Bmp2 deletion results in death by E11.5; embryos are alive at E10.5
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• conditional Bmp2-null embryos are smaller than wild-type controls at E10.5
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• conditional Bmp2-null embryos are smaller than wild-type controls at E10.5
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• at E10.5, embryos have an abnormally patterned heart with an uncharacteristic, straight morphology to the region between the atria and ventricles
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• endocardial cushions and EC mesenchyme are missing at E10.5, as well as the AV constriction
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• some embryos show pericardial effusion
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• some embryos show pericardial effusion
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• some embryos show cardiac edema
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no defects are detected in cardiac morphology or function
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice have normal systolic and diastolic blood pressure at 2, 4, and 10 months of age
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• cardiomyocyte cross-sectional area (CSA) is significantly increased at 2 and 4 months of age
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• after treatment with dexamethasone (DEX), neonatal cardiomyocytes show significantly higher mRNA levels of hypertrophy markers (Nppa, Nppb) and direct glucocorticoid receptor targets (Fkbp5, Tsc22d3), and have a significantly larger surface area than both DEX-treated control cells and untreated cells, indicating increased glucocorticoid-induced cardiomyocyte hypertrophy
• GAS5 overexpression in neonatal cardiomyocytes significantly decreases DEX-induced expression of Nppa (and to a lesser extent of Tsc22d3) and reduces DEX-induced cardiomyocyte hypertrophy by decreasing their surface area
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• whole hearts are overtly enlarged at 10 months of age
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• mice develop LV hypertrophy with significantly increased LV wall thickness, LV mass, cardiomyocyte cross-sectional area, and mRNA levels of heart disease markers Nppb (natriuretic peptide type B, aka Bnp) and Myh7 (myosin, heavy polypeptide 7, cardiac muscle, beta)
• after 2 wks of treatment with DEX, mice show significantly higher mRNA levels of hypertrophy markers (Nppa) and glucocorticoid receptor targets (Fkbp5, Tsc22d3) than both DEX-treated control mice and untreated mice
• GAS5 overexpression via injection of AAV9-GAS5 significantly decreases LV wall thickness and partially reduces expression of Fkbp5 and Tsc22d3 at day 7 post-injection
• however, untreated mice show normal mRNA levels of fibrosis markers and no increase in cardiac fibrosis from 2 to 14 months of age; mRNA and protein expression of Nr3c1 (aka glucocorticoid receptor, GR) is similar to that in control hearts from 2 to 8 months
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• mice show a significant increase in normalized cardiac mass and heart weight to body weight (HW/BW) ratio at 10 and 14 months of age; however, BW is normal from 6 to 14 months of age
• after 2 wks of treatment with DEX, mice show a significantly higher HW/BW ratio than both DEX-treated control mice and untreated mice
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• mice show significantly increased LV mass at 10 and 14 months of age
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• mice show significantly increased left ventricular (LV) wall thickness at 10 and 14 months of age; LV wall is also thicker than that in control Nkx2-5
• 6-wk-old mice treated with DEX for 14 days show a significantly thicker LV wall than both DEX-treated control mice and untreated mice
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• hearts show significantly decreased mRNA levels of Gas5 (growth arrest specific 5), an inhibitor of the glucocorticoid receptor, from P1 to 6 months of age
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• after treatment with a nonsense-mediated decay (NMD) inhibitor, neonatal cardiomyocytes show an even greater increase in Gas5 mRNA levels than similarly treated control cells, suggesting that SRSF4 binds GAS5 and protects it from degradation by NMD
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• mice show progressive diastolic dysfunction, as indicated by a significant and age-dependent reduction in the E/A wave ratio of mitral flow and an elevated isovolumetric relaxation time (IVRT) at 14 months of age
• however, LV ejection fraction (LVEF) and LV diastolic volume (LVVOLd) are normal from 6 to 14 months
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• mice exhibit a significant reduction in the early and late diastolic peak wave ratio (E/A wave ratio of mitral flow) at 14 months of age
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• at 6 months of age, mice exhibit a significantly higher heart rate than controls both under basal and isoproterenol-induced stress conditions
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• under isoproterenol-induced stress conditions, mice exhibit a negative J wave at 6 months of age
• J wave amplitude is also decreased under basal conditions but the difference is not statistically significant
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• under basal conditions, mice exhibit a wider QRS complex amplitude than controls at 6 months of age
• QRS amplitude is also wider under isoproterenol-induced stress conditions but the difference is not statistically significant
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• under isoproterenol-induced stress conditions, mice exhibit a significantly prolonged cQT (= QT interval corrected for heart rate) at 6 months of age
• cQT is also longer under basal conditions but the difference is not statistically significant
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• under isoproterenol-induced stress conditions, mice exhibit a significantly depressed ST-segment at 6 months of age
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• in response to isoproterenol-induced stress, 6-mo-old mice show more severe electrocardiographic features of cardiac hypertrophy and abnormal repolarization, with a further increase in the cQT interval, marked ST-segment depression, and a negative J wave
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• whole hearts are overtly enlarged at 10 months of age
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• mice develop LV hypertrophy with significantly increased LV wall thickness, LV mass, cardiomyocyte cross-sectional area, and mRNA levels of heart disease markers Nppb (natriuretic peptide type B, aka Bnp) and Myh7 (myosin, heavy polypeptide 7, cardiac muscle, beta)
• after 2 wks of treatment with DEX, mice show significantly higher mRNA levels of hypertrophy markers (Nppa) and glucocorticoid receptor targets (Fkbp5, Tsc22d3) than both DEX-treated control mice and untreated mice
• GAS5 overexpression via injection of AAV9-GAS5 significantly decreases LV wall thickness and partially reduces expression of Fkbp5 and Tsc22d3 at day 7 post-injection
• however, untreated mice show normal mRNA levels of fibrosis markers and no increase in cardiac fibrosis from 2 to 14 months of age; mRNA and protein expression of Nr3c1 (aka glucocorticoid receptor, GR) is similar to that in control hearts from 2 to 8 months
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• mice show a significant increase in normalized cardiac mass and heart weight to body weight (HW/BW) ratio at 10 and 14 months of age; however, BW is normal from 6 to 14 months of age
• after 2 wks of treatment with DEX, mice show a significantly higher HW/BW ratio than both DEX-treated control mice and untreated mice
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• cardiomyocyte cross-sectional area (CSA) is significantly increased at 2 and 4 months of age
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• mice develop LV hypertrophy with significantly increased LV wall thickness, LV mass, cardiomyocyte cross-sectional area, and mRNA levels of heart disease markers Nppb (natriuretic peptide type B, aka Bnp) and Myh7 (myosin, heavy polypeptide 7, cardiac muscle, beta)
• after 2 wks of treatment with DEX, mice show significantly higher mRNA levels of hypertrophy markers (Nppa) and glucocorticoid receptor targets (Fkbp5, Tsc22d3) than both DEX-treated control mice and untreated mice
• GAS5 overexpression via injection of AAV9-GAS5 significantly decreases LV wall thickness and partially reduces expression of Fkbp5 and Tsc22d3 at day 7 post-injection
• however, untreated mice show normal mRNA levels of fibrosis markers and no increase in cardiac fibrosis from 2 to 14 months of age; mRNA and protein expression of Nr3c1 (aka glucocorticoid receptor, GR) is similar to that in control hearts from 2 to 8 months
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• in response to isoproterenol-induced stress, 6-mo-old mice show more severe electrocardiographic features of cardiac hypertrophy and abnormal repolarization, with a further increase in the cQT interval, marked ST-segment depression, and a negative J wave
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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 12/10/2024 MGI 6.24 |
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