Phenotypes associated with this allele

• Allele Symbol: Nfatc1^tm1.1(cre)Bz
• Allele Name: targeted mutation 1.1, Bin Zhou
• Allele ID: MGI:5471107
• Summary: 16 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Ccm2^tm1Mlkn/Ccm2^tm1Mlkn Nfatc1^tm1.1(cre)Bz/Nfatc1^+	involves: 129 * 129S1/Sv * 129X1/SvJ	MGI:6279289
cn2	Sox7^tm1.1Nat/Sox7^tm1.1Nat Nfatc1^tm1.1(cre)Bz/Nfatc1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:7550406
cn3	Ift88^tm1Bky/Ift88^tm1Bky Nfatc1^tm1.1(cre)Bz/Nfatc1^+	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ	MGI:6718510
cn4	Nfatc1^tm1.1(cre)Bz/Nfatc1^+ Smarca4^tm1.2Pcn/Smarca4^tm1.2Pcn	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ	MGI:5699720
cn5	Smarca4^tm1.2Pcn/Smarca4^tm1.2Pcn Nfatc1^tm1.1(cre)Bz/Nfatc1^+ Gt(ROSA)26Sor^tm4(ACTB-tdTomato,-EGFP)Luo/Gt(ROSA)26Sor^+	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ	MGI:5699724
cn6	Kdr^tm1Wag/Kdr^tm1Wag Nfatc1^tm1.1(cre)Bz/Nfatc1^+ Gt(ROSA)26Sor^tm1Sor/Gt(ROSA)26Sor^+	involves: 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6	MGI:5471122
cn7	Nfatc1^tm1.1(cre)Bz/Nfatc1^+ Sema6d^tm1.1Jiao/Sema6d^tm1.1Jiao	involves: 129S1/Sv * 129S6/SvEvTac * 129X1/Sv * C57BL/6	MGI:6358309
cn8	Tbx20^tm1Sev/Tbx20^tm1.1Sev Nfatc1^tm1.1(cre)Bz/Nfatc1^+	involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * Black Swiss	MGI:5524038
cn9	Krit1^tm1Kwhi/Krit1^tm1Kwhi Nfatc1^tm1.1(cre)Bz/Nfatc1^+	involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6NCrl	MGI:6279286
cn10	Krit1^tm1Kwhi/Krit1^tm1Kwhi Map3k3^tm1.1Mlkn/Map3k3^+ Nfatc1^tm1.1(cre)Bz/Nfatc1^+	involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6NCrl * C57BL/6NTac	MGI:6279292
cn11	Pdcd10^tm1Kwhi/Pdcd10^tm1Kwhi Nfatc1^tm1.1(cre)Bz/Nfatc1^+	involves: 129S1/Sv * 129X1/SvJ	MGI:6279290
cn12	Kdr^tm1Wag/Kdr^tm1Wag Nfatc1^tm1.1(cre)Bz/Nfatc1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5471121
cn13	Adgrg6^em3Jlp/Adgrg6^em3Jlp Nfatc1^tm1.1(cre)Bz/Nfatc1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:7442262
cn14	Creld1^tm1c(EUCOMM)Wtsi/Creld1^tm1c(EUCOMM)Wtsi Nfatc1^tm1.1(cre)Bz/Nfatc1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/6N * SJL	MGI:7546787
cn15	Dzip1^tm1Sasl/Dzip1^tm1Sasl Nfatc1^tm1.1(cre)Bz/Nfatc1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:6718507
cn16	Map3k3^tm1.1Mlkn/Map3k3^tm1.2Mlkn Nfatc1^tm1.1(cre)Bz/Nfatc1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6NTac	MGI:6279295

Genotype
MGI:6279289

cn1

• Allelic Composition: Ccm2^tm1Mlkn/Ccm2^tm1Mlkn; Nfatc1^tm1.1(cre)Bz/Nfatc1⁺
• Genetic Background: involves: 129 * 129S1/Sv * 129X1/SvJ

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:238897 )

• embryonic lethality at E14.5-E15.5

cardiovascular system

thin myocardium ( J:238897 )

• embryos exhibit a reduction in myocardial growth at E10.5

decreased cardiac jelly amount ( J:238897 )

• embryos exhibit a reduction in cardiac jelly at E10.5 as indicated by reduced matrix glycosaminoglycans and versican in the heart

muscle

thin myocardium ( J:238897 )

• embryos exhibit a reduction in myocardial growth at E10.5

Genotype
MGI:7550406

cn2

• Allelic Composition: Sox7^tm1.1Nat/Sox7^tm1.1Nat; Nfatc1^tm1.1(cre)Bz/Nfatc1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

mortality/aging

mortality/aging ( J:306193 )

N • mice are reported to survive after birth (no postnatal stage provided)

cardiovascular system

abnormal cardiac epithelial to mesenchymal transition ( J:306193 )

• 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

atrioventricular cushion hypoplasia ( J:306193 )

• 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

atrial septal defect ( J:306193 )

• at E14.5, 44.4% (4/9) of embryos show defects in closure of the atrial septum (ASD)

partial atrioventricular septal defect ( J:306193 )

abnormal interventricular septum morphology ( J:306193 )

• 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

embryo

embryo phenotype ( J:306193 )

N • embryos show no major changes in somite number at E9.5 and appear grossly normal at E10.5

Genotype
MGI:6718510

cn3

• Allelic Composition: Ift88^tm1Bky/Ift88^tm1Bky; Nfatc1^tm1.1(cre)Bz/Nfatc1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ

cardiovascular system

abnormal mitral valve morphology ( J:291454 )

• failure of ciliogenesis with lack of axonemes in valve mesenchyme

• adult mice exhibit myxomatous mitral valve disease with loss of normal extracellular matrix distribution

abnormal mitral valve cusp morphology ( J:291454 )

• enlarged at P0

• however, mice exhibit normal proliferation and total number of valve progenitor cells

cellular

abnormal motile cilium morphology ( J:291454 )

• 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

Genotype
MGI:5699720

cn4

• Allelic Composition: Nfatc1^tm1.1(cre)Bz/Nfatc1⁺; Smarca4^tm1.2Pcn/Smarca4^tm1.2Pcn
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:226941 )

• a decrease in fraction of viable mutants is first seen at E16.5, with few surviving after birth

perinatal lethality ( J:226941 )

• only 3% of the expected 25% of mice are seen at weaning and mice rarely survive to adulthood

cardiovascular system

abnormal aortic sinus morphology ( J:226941 )

• E16.5 aortic valves lack the typical extended aortic sinuses seen in wild-type littermates

abnormal coronary artery morphology ( J:226941 )

• coronary artery network is reduced in rare viable P0 pups

abnormal coronary vein morphology ( J:226941 )

• mutants have dilated coronary veins at P0

thick myocardium ( J:226941 )

• hearts from rare viable P0 pups have a thickened compact myocardium

abnormal cardiac outflow tract development ( J:226941 )

• 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

perimembraneous ventricular septal defect ( J:226941 )

• E14.5 mutants occasionally have a small membranous ventricular septal defect which usually resolves by E16.5 in surviving mutants

enlarged heart ( J:226941 )

• hearts from rare viable P0 pups are larger

abnormal semilunar valve morphology ( J:226941 )

• 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

abnormal aortic valve morphology ( J:226941 )

• 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

abnormal aortic valve cusp morphology ( J:226941 )

• E16.5 aortic valves lack the typical thin elongated cusps seen in wild-type littermates

bicuspid aortic valve ( J:226941 )

• 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

thick aortic valve ( J:226941 )

• hearts from newborns have thickened aortic valves

abnormal pulmonary valve cusp morphology ( J:226941 )

• 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

thick pulmonary valve ( J:226941 )

• hearts from newborns have thickened pulmonic valves

thick heart valve cusps ( J:226941 )

• semilunar valve cusps are thickened and poorly elongated at E16.5

growth/size/body

enlarged heart ( J:226941 )

• hearts from rare viable P0 pups are larger

muscle

thick myocardium ( J:226941 )

• hearts from rare viable P0 pups have a thickened compact myocardium

Genotype
MGI:5699724

cn5

• Allelic Composition: Smarca4^tm1.2Pcn/Smarca4^tm1.2Pcn; Nfatc1^tm1.1(cre)Bz/Nfatc1⁺; Gt(ROSA)26Sor^{tm4(ACTB-tdTomato,-EGFP)Luo}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ

cardiovascular system

abnormal semilunar valve morphology ( J:226941 )

• semilunar valves have reduced endocardial-derived mesenchyme

• 2-fold increase in EdU-incorporated mesenchymal cells, indicating increased proliferation of cushion mesenchyme

Genotype
MGI:5471122

cn6

• Allelic Composition: Kdr^tm1Wag/Kdr^tm1Wag; Nfatc1^tm1.1(cre)Bz/Nfatc1⁺; Gt(ROSA)26Sor^tm1Sor/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6

cardiovascular system

abnormal coronary artery morphology ( J:193198 )

• embryos do not develop intramyocardial coronary arteries

abnormal angiogenesis ( J:193198 )

• at E11.5, endocardial cells cannot respond to Vegf120 and fail to migrate, sprout, and form endothelial networks

Genotype
MGI:6358309

cn7

• Allelic Composition: Nfatc1^tm1.1(cre)Bz/Nfatc1⁺; Sema6d^tm1.1Jiao/Sema6d^tm1.1Jiao
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * 129X1/Sv * C57BL/6

cardiovascular system

abnormal cardiac epithelial to mesenchymal transition ( J:254695 )

• 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)

abnormal atrioventricular cushion morphology ( J:254695 )

• 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

Genotype
MGI:5524038

cn8

• Allelic Composition: Tbx20^tm1Sev/Tbx20^tm1.1Sev; Nfatc1^tm1.1(cre)Bz/Nfatc1⁺
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * Black Swiss

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:198628 )

• embryos die between E14.5 and E16.5

cardiovascular system

decreased atrioventricular cushion size ( J:198628 )

• smaller in size

• pulmonary and aortic valve cushions are normal in size at E12.5

abnormal heart valve morphology ( J:198628 )

• 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

small atrioventricular valve ( J:198628 )

• mitral and tricuspid valves are much shorter than controls

small semilunar valve ( J:198628 )

• semilunar valves are 66 or 69% of the control length

abnormal cardiovascular system physiology ( J:198628 )

hemorrhage ( J:198628 )

• peripheral hemorrhage in most embryos at E15.5

aortic valve regurgitation ( J:198628 )

• significant at E14.5

Genotype
MGI:6279286

cn9

• Allelic Composition: Krit1^tm1Kwhi/Krit1^tm1Kwhi; Nfatc1^tm1.1(cre)Bz/Nfatc1⁺
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6NCrl

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:238897 )

• mice die prior to birth, with all embryos dead by E14.5-E15.5

cardiovascular system

abnormal heart morphology ( J:238897 )

• 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

abnormal myocardial trabeculae morphology ( J:238897 )

• E10.5 hearts exhibit smaller myocardial trabeculae

thin myocardium ( J:238897 )

• myocardium is thin at E10.5

decreased cardiac jelly amount ( J:238897 )

• 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

dilated heart atrium ( J:238897 )

• atrial dilatation is seen at E12.5

dilated heart ventricle ( J:238897 )

• ventricular chamber dilatation is seen at E12.5

muscle

abnormal myocardial trabeculae morphology ( J:238897 )

• E10.5 hearts exhibit smaller myocardial trabeculae

thin myocardium ( J:238897 )

• myocardium is thin at E10.5

Genotype
MGI:6279292

cn10

• Allelic Composition: Krit1^tm1Kwhi/Krit1^tm1Kwhi; Map3k3^tm1.1Mlkn/Map3k3⁺; Nfatc1^tm1.1(cre)Bz/Nfatc1⁺
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6NCrl * C57BL/6NTac

cardiovascular system

decreased cardiac jelly amount ( J:238897 )

• area occupied by cardiac jelly in the trabeculae is decreased only 25% at E10.5, indicating some rescue of cardiac jelly

Genotype
MGI:6279290

cn11

• Allelic Composition: Pdcd10^tm1Kwhi/Pdcd10^tm1Kwhi; Nfatc1^tm1.1(cre)Bz/Nfatc1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:238897 )

• embryonic lethality, with all fetuses dead by E15.5-E17.5

cardiovascular system

thin myocardium ( J:238897 )

• embryos exhibit a reduction in myocardial growth at E12.5

abnormal cardiac jelly morphology ( J:238897 )

• embryos exhibit reduced cardiac jelly at E12.5 as indicated by reduced matrix glycosaminoglycans and versican in the heart

muscle

thin myocardium ( J:238897 )

• embryos exhibit a reduction in myocardial growth at E12.5

Genotype
MGI:5471121

cn12

• Allelic Composition: Kdr^tm1Wag/Kdr^tm1Wag; Nfatc1^tm1.1(cre)Bz/Nfatc1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:193198 )

• all die prior to birth (after or during E14.5-16.5)

growth/size/body

decreased body size ( J:193198 )

• observed after E14.5 through 16.5

cardiovascular system

abnormal coronary artery morphology ( J:193198 )

• E14.5 embryos have severely diminished or absent coronary arteries, but coronary veins develop

abnormal angiogenesis ( J:193198 )

• 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

abnormal interventricular septum morphology ( J:193198 )

• E12.5 mutants do not develop coronary plexuses in the ventricular septum

heart hemorrhage ( J:193198 )

• embryos develop cardiac hemorrhages at E14.5-16.5

Genotype
MGI:7442262

cn13

• Allelic Composition: Adgrg6^em3Jlp/Adgrg6^em3Jlp; Nfatc1^tm1.1(cre)Bz/Nfatc1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

normal phenotype

no abnormal phenotype detected ( J:315981 )

• unexpectedly, mice are viable throughout embryogenesis with no resorptions observed from E11.5 to E18.5 and no cardiac abnormalities detected at E15.5

Genotype
MGI:7546787

cn14

• Allelic Composition: Creld1^{tm1c(EUCOMM)Wtsi}/Creld1^{tm1c(EUCOMM)Wtsi}; Nfatc1^tm1.1(cre)Bz/Nfatc1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/6N * SJL

normal phenotype

no abnormal phenotype detected ( J:304446 )

• mice are recovered at Mendelian ratios at 3 weeks of age and do not exhibit an overt cardiac phenotype

Genotype
MGI:6718507

cn15

• Allelic Composition: Dzip1^tm1Sasl/Dzip1^tm1Sasl; Nfatc1^tm1.1(cre)Bz/Nfatc1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

cardiovascular system

abnormal mitral valve morphology ( J:291454 )

• reduced cilia length in valve mesenchyme

• adult mice exhibit myxomatous mitral valves with loss of normal extracellular matrix distribution

abnormal mitral valve cusp morphology ( J:291454 )

• elongated leaflet

mitral valve prolapse ( J:291454 )

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

Genotype
MGI:6279295

cn16

• Allelic Composition: Map3k3^tm1.1Mlkn/Map3k3^tm1.2Mlkn; Nfatc1^tm1.1(cre)Bz/Nfatc1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6NTac

mortality/aging

embryonic lethality during organogenesis ( J:238897 )

• embryonic lethality prior to E12.5

cardiovascular system

thin myocardium ( J:238897 )

• thin myocardial cell layer

• however, cardiac jelly is preserved and endocardial-myocardial separation at E10.5 is normal

muscle

thin myocardium ( J:238897 )

• thin myocardial cell layer

• however, cardiac jelly is preserved and endocardial-myocardial separation at E10.5 is normal