Analysis Tools|
Allele Symbol Allele Name Allele ID |
Nfatc1+ wild type MGI:2432954 |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Summary |
18 genotypes
|
|
|
Data Sources
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• embryonic lethality at E14.5-E15.5
|
|
• embryos exhibit a reduction in myocardial growth at E10.5
|
|
• embryos exhibit a reduction in cardiac jelly at E10.5 as indicated by reduced matrix glycosaminoglycans and versican in the heart
|
|
• embryos exhibit a reduction in myocardial growth at E10.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• failure of ciliogenesis with lack of axonemes in valve mesenchyme
• adult mice exhibit myxomatous mitral valve disease with loss of normal extracellular matrix distribution
|
|
• enlarged at P0
• however, mice exhibit normal proliferation and total number of valve progenitor cells
|
|
• failure of ciliogenesis with lack of axonemes in valve mesenchyme
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| mitral valve disease | DOID:61 | J:291454 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• most mice have a normal lifespan
|
|
• hearts are frequently enlarged with thickened ventricles
|
|
• thickened ventricles
|
|
• aortic valves have myxomatous characteristics, with extensive proteoglycan-rich material throughout the valve and intermittent and dispersed collagen deposits rather than the typical enrichment of collagen along the atrial side of the cusps
• aortic valves show presence of irregular chondrocyte-like cells with large nuclei and scattered small-nucleated cells, especially at the lateral edges of the cusps where they contact neighboring muscle
|
|
• 9 of 26 mice have a bicuspid aortic valve
|
|
• adults frequently (21 of 26) have thickened aortic valve cusps
|
|
• pulmonic valves are thickened
• however, the mitral valve is normal
|
|
• mice exhibit aortic valve disease with thickened, misorganized and myxomatous cusps, bicuspid arrangement formation usually arising from left coronary cusp-non-coronary cusp fusion, without calcification
|
|
• mice exhibit aortic valve disease with thickened, misorganized and myxomatous cusps, bicuspid arrangement formation usually arising from left coronary cusp-non-coronary cusp fusion, without calcification
|
|
• hearts are frequently enlarged with thickened ventricles
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• semilunar valves have reduced endocardial-derived mesenchyme
• 2-fold increase in EdU-incorporated mesenchymal cells, indicating increased proliferation of cushion mesenchyme
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• a decrease in fraction of viable mutants is first seen at E16.5, with few surviving after birth
|
|
• only 3% of the expected 25% of mice are seen at weaning and mice rarely survive to adulthood
|
|
• E16.5 aortic valves lack the typical extended aortic sinuses seen in wild-type littermates
|
|
• coronary artery network is reduced in rare viable P0 pups
|
|
• mutants have dilated coronary veins at P0
|
|
• hearts from rare viable P0 pups have a thickened compact myocardium
|
|
• the proximal outflow tract, but not the neural crest cell-populated distal outflow tract, cushion contains about half the normal number of mesenchymal cells at E10.5, less than 24 hours after endocardial-to-mesenchymal trasnformation onset
|
|
• E14.5 mutants occasionally have a small membranous ventricular septal defect which usually resolves by E16.5 in surviving mutants
|
|
• hearts from rare viable P0 pups are larger
|
|
• the thinner hinge region that demarcates the boundary between the distal and basal regions of each cusp of both aortic and pulmonic valves is absent at E16.5
• semilunar valve defects first become apparent at E14.5 as a decreased length:width ratio of the forming cusps
• expression analysis at E16.5 shows mislocalized extracellular matrix indicating a loss of patterning of the semilunar valve cusps into distinct base and distal regions
• however, the mitral valve is normal
|
|
• aortic valves of rare survivors have myxomatous characteristics, with extensive proteoglycan-rich material throughout the valve and intermittent and dispersed collagen deposits rather than the typical enrichment of collagen along the atrial side of the cusps
• however, little or no change in calcification of aortic valves in rare surviving mice is seen
• rare survivors exhibit aortic valve disease with thickened, misorganized and myxomatous cusps, and bicuspid arrangement formation usually arising from left coronary cusp-non-coronary cusp fusion, without calcification
|
|
• E16.5 aortic valves lack the typical thin elongated cusps seen in wild-type littermates
|
|
• 3 of 6 mutants exhibit bicuspid aortic valves: the bicuspid valve originates from a fusion between the left and non-coronary cusps, with residual individual cusp attachment points to the surrounding muscle
|
|
• hearts from newborns have thickened aortic valves
|
|
• the left and right cusps of the pulmonic valve have decreased length:width ratios, are increased in area, and have a modest increase in the number of interstitial cells per valve section at E16.5
|
|
• hearts from newborns have thickened pulmonic valves
|
|
• semilunar valve cusps are thickened and poorly elongated at E16.5
|
|
• hearts from rare viable P0 pups are larger
|
|
• hearts from rare viable P0 pups have a thickened compact myocardium
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• embryos do not develop intramyocardial coronary arteries
|
|
• at E11.5, endocardial cells cannot respond to Vegf120 and fail to migrate, sprout, and form endothelial networks
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the percentage of endocardial cells undergoing epithelial-mesenchymal-transition (EMT) in atrioventricular cushions is reduced at E9.25 but is increased at later stages (E9.5 and E10.5)
|
|
• hypocellular atrioventricular cushion at E9.25 is caused by reduced mesenchyme formation, with the number of mesenchymal cells in atrioventricular cushions reduced to about 30% of the control level at the initial stage of cushion mesenchymal cell formation (about E9.5)
• however, by E10.5, this difference in number of mesenchymal cells is no longer seen, no morphological defect is seen in adult valves and echocardiography analysis does not show any functional abnormalities in the atrioventricular valves
• the number of mesenchymal cells formed from atrioventricular cushion explants is reduced
• expression of Sema6C is increased in atrioventricular cushions, in both endocardial and mesenchymal cells, starting from E9.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• embryos die between E14.5 and E16.5
|
|
• smaller in size
• pulmonary and aortic valve cushions are normal in size at E12.5
|
|
• heart valve leaflets are shorter and blunt relative to controls
• all heart valves are similarly affected at E14.5
• endocardial cell proliferation in all valves is much reduced while mesenchymal cell proliferation is unchanged
• little apoptosis
|
|
• mitral and tricuspid valves are much shorter than controls
|
|
• semilunar valves are 66 or 69% of the control length
|
|
• peripheral hemorrhage in most embryos at E15.5
|
|
• significant at E14.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die prior to birth, with all embryos dead by E14.5-E15.5
|
|
• hearts show a reduction in space between the endocardium and myocardium that is occupied by cardiac jelly at E10.5 and E12.5
• in the myocardial trabeculae, the myocardium is wrapped tightly by endocardium unlike in wild-type mice where it is separated from the endocardium, indicating loss of endocardial-myocardial separation
|
|
• E10.5 hearts exhibit smaller myocardial trabeculae
|
|
• myocardium is thin at E10.5
|
|
• area occupied by cardiac jelly in the trabeculae is decreased more than 65% at E10.5
• loss of matrix glycosaminoglycans in the heart, particularly surrounding the trabeculae at E10.5 and loss of intact versican indicates a reduction in cardiac jelly
|
|
• atrial dilatation is seen at E12.5
|
|
• ventricular chamber dilatation is seen at E12.5
|
|
• E10.5 hearts exhibit smaller myocardial trabeculae
|
|
• myocardium is thin at E10.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• area occupied by cardiac jelly in the trabeculae is decreased only 25% at E10.5, indicating some rescue of cardiac jelly
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• embryonic lethality, with all fetuses dead by E15.5-E17.5
|
|
• embryos exhibit a reduction in myocardial growth at E12.5
|
|
• embryos exhibit reduced cardiac jelly at E12.5 as indicated by reduced matrix glycosaminoglycans and versican in the heart
|
|
• embryos exhibit a reduction in myocardial growth at E12.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all die prior to birth (after or during E14.5-16.5)
|
|
• observed after E14.5 through 16.5
|
|
• E14.5 embryos have severely diminished or absent coronary arteries, but coronary veins develop
|
|
• a 24% reduction of subepicardial endothelial cell population (for vein formation) is detected at E14.5, with a 74% decrease in intramyocardial endothelial cells (for artery formation) detected
• E12.5 mutants do not develop coronary plexuses in the peritruncal/coronary sulcus area or ventricular septum
|
|
• E12.5 mutants do not develop coronary plexuses in the ventricular septum
|
|
• embryos develop cardiac hemorrhages at E14.5-16.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• unexpectedly, mice are viable throughout embryogenesis with no resorptions observed from E11.5 to E18.5 and no cardiac abnormalities detected at E15.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice are recovered at Mendelian ratios at 3 weeks of age and do not exhibit an overt cardiac phenotype
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduced cilia length in valve mesenchyme
• adult mice exhibit myxomatous mitral valves with loss of normal extracellular matrix distribution
|
|
• elongated leaflet
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| mitral valve prolapse | DOID:988 |
OMIM:157700 OMIM:607829 OMIM:610840 |
J:291454 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• embryonic lethality prior to E12.5
|
|
• thin myocardial cell layer
• however, cardiac jelly is preserved and endocardial-myocardial separation at E10.5 is normal
|
|
• thin myocardial cell layer
• however, cardiac jelly is preserved and endocardial-myocardial separation at E10.5 is normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice are reported to survive after birth (no postnatal stage provided)
|
|
• at E9.5, E10.5, and E11.5, atrioventricular (AV) cushions exhibit significantly lower numbers of mesenchymal cells than control cushions, suggesting disruption of endothelial to mesenchymal transition (EndMT)
• at E9.5, expression of AV cushion EndMT markers Snai1, Sox9, and Has2 is reduced in atrioventricular canals (AVCs), whereas Notch1 expression remains normal
• expression of Wnt4 in endocardium and of Bmp2 and its target Tbx2 in myocardium is reduced in AVCs at E9.5, whereas Tbx20 expression remains normal
• levels of phosphorylated-Smad1/5/8 (pSmad1/5/8) are significantly decreased in AV cushions at E10.5
• in vitro 3D collagen gel assays show that AVC explants from E9.5 embryos exhibit a significantly lower number of mesenchymal cells that migrate and invade into the matrix than control explants, indicating impaired EndMT
• addition of recombinant WNT4 or BMP2 protein partially rescues the EndMT defect, and inhibition of BMP2 with Noggin attenuates rescue of impaired EndMT by WNT4 protein, suggesting that Sox7 can regulate EndMT through Wnt4-Bmp2 signaling
|
|
• at E9.5, E10.5, and E11.5, atrioventricular (AV) cushions exhibit significantly lower numbers of mesenchymal cells than control cushions
• at E9.5, AV cushions show significantly reduced glycosaminoglycans, indicating impaired extracellular matrix (ECM) formation
• hypocellular cushion phenotype is at least partly due to reduced endocardial cell proliferation: at E9.5, AV cushions show a sharp decrease in the number of KI67+ endocardial cells; the number of PCNA+ endocardial cells is much lower than that in control cushions
• KI67 staining shows reduced mesenchymal cell proliferation in AV cushions at E10.5
• however, no change in endocardial cell apoptosis is noted at E9.5, E11.5 and E14.5
|
|
• at E14.5, 44.4% (4/9) of embryos show defects in closure of the atrial septum (ASD)
|
|
• at E13.5, 63.6% (7/11) of embryos exhibit incomplete fusion or developmental delay of contact of the developing ventricular septum with the cardiac cushion versus 14.3% (1/7) of control embryos
|
| N |
• embryos show no major changes in somite number at E9.5 and appear grossly normal at E10.5
|
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
||
|
Citing These Resources Funding Information Warranty Disclaimer, Privacy Notice, Licensing, & Copyright Send questions and comments to User Support. |
last database update 12/30/2025 MGI 6.24 |
|
|
|
||
