Phenotypes associated with this allele

• Allele Symbol: Nkx2-5^tm1(cre)Rjs
• Allele Name: targeted mutation 1, Robert J Schwartz
• Allele ID: MGI:2654594
• Summary: 44 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Smarcd3^tm1.1Bbr/Smarcd3^tm1.1Bbr Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	either: (involves: 129 * C57BL/6 * SJL) or (involves: 129 * C57BL/6 * ICR * SJL)	MGI:6368032
cn2	Gt(ROSA)26Sor^tm1(DTA)Jpmb/Gt(ROSA)26Sor^+ Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	either: (involves: 129S/SvEv * 129S7/SvEvBrd * C57BL/6) or (involves: 129S/SvEv * 129S7/SvEvBrd * CD-1)	MGI:3611572
cn3	Bnip3l^tm1Gwd/Bnip3l^tm1Gwd Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129 * 129S7/SvEvBrd	MGI:4430398
cn4	Fgf8^tm1.3Mrt/Fgf8^tm2Mrt Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129 * 129S7/SvEvBrd	MGI:3818073
cn5	Dicer1^tm1Bdh/Dicer1^tm1Bdh Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129 * 129S7/SvEvBrd * C57BL/6	MGI:5575766
cn6	Atoh8^tm1.1Mlkn/Atoh8^tm1.1Mlkn Gata4^tm1.1Sad/Gata4^+ Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129 * C57BL/6	MGI:5532942
cn7	Foxp1^tm2.1Eem/Foxp1^tm2.1Eem Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129 * C57BL/6 * SJL	MGI:4829788
cn8	Fgf8^tm1.3Mrt/Fgf8^tm1.4Mrt Gt(ROSA)26Sor^tm1Sor/Gt(ROSA)26Sor^tm1Sor Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129P2/OlaHsd * 129S4/SvJaeSor * 129S7/SvEvBrd	MGI:3818077
cn9	Hic2^Gt(E225A08)1.1Wrst/Hic2^Gt(E225A08)1.1Wrst Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129P2/OlaHsd * 129S7/SvEvBrd	MGI:5707467
cn10	Fgf8^tm1.3Mrt/Fgf8^tm1.4Mrt Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129P2/OlaHsd * 129S7/SvEvBrd	MGI:3818072
cn11	Casz1^tm1.1Flc/Casz1^+ Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * C57BL/6J * SJL	MGI:5811817
cn12	Casz1^tm1.1Flc/Casz1^tm1.1Flc Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * C57BL/6J * SJL	MGI:5811822
cn13	Daam1^Gt(RRT390)Byg/Daam1^Gt(RRT390)Byg Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6J	MGI:4880768
cn14	Daam1^tm1.1Tpy/Daam1^tm1.1Tpy Gt(ROSA)26Sor^tm1Sor/Gt(ROSA)26Sor^+ Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S1/Sv * 129S4/SvJaeSor * 129S7/SvEvBrd	MGI:6150944
cn15	Prox1^tm2Gco/Prox1^tm2Gco Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S1/Sv * 129S7/SvEvBrd	MGI:5907122
cn16	Daam1^tm1.1Tpy/Daam1^tm1.1Tpy Nkx2-5^tm1(cre)Rjs/Nkx2-5^+ Wnt5a^tm1Amc/Wnt5a^+	involves: 129S1/Sv * 129S7/SvEvBrd	MGI:6151066
cn17	Daam1^tm1.1Tpy/Daam1^tm1.1Tpy Nkx2-5^tm1(cre)Rjs/Nkx2-5^+ Wnt5a^tm1Amc/Wnt5a^tm1Amc	involves: 129S1/Sv * 129S7/SvEvBrd	MGI:6150926
cn18	Daam1^tm1.1Tpy/Daam1^tm1.1Tpy Daam2^tm1Tpy/Daam2^tm1Tpy Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S1/Sv * 129S7/SvEvBrd	MGI:6150919
cn19	Daam1^tm1.1Tpy/Daam1^tm1.1Tpy Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S1/Sv * 129S7/SvEvBrd	MGI:6150918
cn20	Zfpm2^tm1Sho/Zfpm2^tm2Sho Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S1/Sv * 129S7/SvEvBrd	MGI:3851399
cn21	Shh^tm1Chg/Shh^tm2Amc Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ	MGI:4843919
cn22	Hspb7^tm1.1Chen/Hspb7^tm1.1Chen Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ * C57BL/6	MGI:6159009
cn23	Gata4^tm1.1Sad/Gata4^tm1.1Sad Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:3783262
cn24	Bmp2^tm1Jfm/Bmp2^tm1Jfm Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S4/SvJaeSor	MGI:3620974
cn25	Bmp4^tm1Jfm/Bmp4^tm1.1Jfm Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S4/SvJaeSor * 129S7/SvEvBrd	MGI:3043044
cn26	Grk2^tm1Gwd/Grk2^tm1Gwd Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S4/SvJaeSor * 129S7/SvEvBrd * C57BL/6	MGI:3763210
cn27	Nkx2-5^tm1(cre)Rjs/Nkx2-5^+ Zic3^tm2.1Jwb/Y	involves: 129S4/SvJaeSor * 129S7/SvEvBrd * C57BL/6J	MGI:5470169
cn28	Gata4^tm1Sho/Gata4^tm1.1Wtp Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S6/SvEvTac * 129S7/SvEvBrd	MGI:3851408
cn29	Gata4^tm1Sho/Gata4^+ Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S6/SvEvTac * 129S7/SvEvBrd	MGI:3851410
cn30	Fkbp1a^tm1.1Shou/Fkbp1a^tm1Zuk Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S7/SvEvBrd	MGI:5490242
cn31	Gata4^tm1.1Wtp/Gata4^tm1.1Wtp Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S7/SvEvBrd	MGI:3639276
cn32	Zic3^tm1.1Smwa/Y Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S7/SvEvBrd	MGI:5476840
cn33	Hand1^tm5Abfi/Hand1^+ Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S7/SvEvBrd	MGI:6766587
cn34	Ehmt1^tm2Yshk/Ehmt1^tm2Yshk Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S7/SvEvBrd	MGI:5543776
cn35	Smo^tm2Amc/Smo^tm2.1Amc Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S7/SvEvBrd * 129X1/SvJ	MGI:4843927
cn36	Frs2^tm1Fwan/Frs2^tm1Fwan Nkx2-5^tm1(cre)Rjs/?	involves: 129S7/SvEvBrd * C57BL/6	MGI:3768916
cn37	Nkx2-5^tm1(cre)Rjs/Nkx2-5^+ Tbx1^tm1Bld/Tbx1^tm3Bld	involves: 129S7/SvEvBrd * C57BL/6	MGI:3046805
cn38	Gt(ROSA)26Sor^tm1.1(CAG-Mirc20)Eem/Gt(ROSA)26Sor^+ Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S7/SvEvBrd * C57BL/6	MGI:5792841
cn39	Foxc2^tm1.1Miu/Foxc2^tm1.1Miu Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S7/SvEvBrd * C57BL/6 * C57BL/6J * SJL	MGI:6879488
cn40	Adam17^tm1.1Wesh/Adam17^tm1.1Wesh Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S7/SvEvBrd * C57BL/6 * FVB/N	MGI:5571466
cn41	Akap6^tm1.1Mskf/Akap6^tm1.1Mskf Nkx2-5^tm1(cre)Rjs/0	involves: 129S7/SvEvBrd * C57BL/6 * SJL	MGI:5603566
cn42	Yap1^tm1.1Eno/Yap1^tm1.1Eno Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S/SvEv	MGI:5446510
cx43	Nipbl^Gt(RRS564)Byg/Nipbl^+ Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129P2/OlaHsd * 129S7/SvEvBrd * CD-1	MGI:7492254
cx44	Nkx2-5^tm1(cre)Rjs/Nkx2-5^+ Nsd2^tm1Ykan/Nsd2^+	involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6	MGI:3851519

Genotype
MGI:6368032

cn1

• Allelic Composition: Smarcd3^tm1.1Bbr/Smarcd3^tm1.1Bbr; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: either: (involves: 129 * C57BL/6 * SJL) or (involves: 129 * C57BL/6 * ICR * SJL)

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

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:257963 )

• no live embryos are recovered after E14.5

cardiovascular system

abnormal myocardial trabeculae morphology ( J:257963 )

• reduced trabeculation at E14.5

thin myocardium ( J:257963 )

• thin myocardium at E14.5

abnormal interventricular septum morphology ( J:257963 )

• ventricular septum is thinner and is poorly organized by E14.5

thin ventricular wall ( J:257963 )

• ventricle free walls are thinner by E14.5

muscle

abnormal myocardial trabeculae morphology ( J:257963 )

• reduced trabeculation at E14.5

thin myocardium ( J:257963 )

• thin myocardium at E14.5

Genotype
MGI:3611572

cn2

• Allelic Composition: Gt(ROSA)26Sor^tm1(DTA)Jpmb/Gt(ROSA)26Sor⁺; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: either: (involves: 129S/SvEv * 129S7/SvEvBrd * C57BL/6) or (involves: 129S/SvEv * 129S7/SvEvBrd * CD-1)

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:103417 )

• lethality occurs around E9.5

cardiovascular system

absent heart ( J:103417 )

• at the 12-14 somite stage no heart is present

embryo

decreased embryo size ( J:103417 )

• at E9.5 embryos are very small and some are partially resorbed

growth/size/body

decreased embryo size ( J:103417 )

• at E9.5 embryos are very small and some are partially resorbed

Genotype
MGI:4430398

cn3

• Allelic Composition: Bnip3l^tm1Gwd/Bnip3l^tm1Gwd; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129 * 129S7/SvEvBrd

cardiovascular system

abnormal heart left ventricle morphology ( J:145086 )

• late after pressure overload, mice exhibit reduced left ventricular end-diastolic diameter, left ventricular dilation, and ventricular remodeling compared with similarly treated wild-type mice

cardiac fibrosis ( J:145086 )

• 9 weeks after pressure overload compared with similarly treated wild-type mice

increased cardiac muscle contractility ( J:145086 )

• late after pressure overload compared with similarly treated wild-type mice

decreased cardiomyocyte apoptosis ( J:145086 )

• 9 weeks after pressure overload compared with similarly treated wild-type mice

abnormal response of heart to induced stress ( J:145086 )

• late after pressure overload, mice exhibit increased myocardial contractile function and velocity of circumferential shortening and reduced left ventricular end-diastolic diameter, left ventricular dilation, ventricular remodeling, myocardial fibrosis, and cardiomyocyte apoptosis compared with similarly treated wild-type mice

• however, hypertrophic response to pressure overload is normal

homeostasis/metabolism

abnormal response of heart to induced stress ( J:145086 )

• late after pressure overload, mice exhibit increased myocardial contractile function and velocity of circumferential shortening and reduced left ventricular end-diastolic diameter, left ventricular dilation, ventricular remodeling, myocardial fibrosis, and cardiomyocyte apoptosis compared with similarly treated wild-type mice

• however, hypertrophic response to pressure overload is normal

muscle

increased cardiac muscle contractility ( J:145086 )

• late after pressure overload compared with similarly treated wild-type mice

decreased cardiomyocyte apoptosis ( J:145086 )

• 9 weeks after pressure overload compared with similarly treated wild-type mice

cellular

decreased cardiomyocyte apoptosis ( J:145086 )

• 9 weeks after pressure overload compared with similarly treated wild-type mice

Genotype
MGI:3818073

cn4

• Allelic Composition: Fgf8^tm1.3Mrt/Fgf8^tm2Mrt; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129 * 129S7/SvEvBrd

mortality/aging

mortality/aging ( J:109474 )

N • phenotype is stated to be identical to that of Fgf8^tm1.3Mrt/ Fgf8^tm1.4Mrt; Nkx2-5^tm1(cre)Rjs/ Nkx2-5⁺ mutants; however no data are presented

embryo

abnormal pharyngeal arch morphology ( J:109474 )

• at E9.5 cell proliferation in pharyngeal endoderm is reduced with cell mitotic indices decreased by 60% relative to controls

abnormal pharyngeal arch mesenchyme morphology ( J:109474 )

• excessive neural crest cell death is observed in pharyngeal arch mesenchyme at E9.5

abnormal splanchnic mesoderm morphology ( J:109474 )

• thinning of splanchnic mesoderm (SM) layers

• at E9.5 cell proliferation in SM is reduced with cell mitotic indices decreased by 50% relative to controls

• excessive cell death is detected from E8.5-9.5 in SM immediately distal to emerging outflow tract and in endoderm adjacent to the SM

abnormal neural crest cell morphology ( J:109474 )

• excessive neural crest cell death is observed in pharyngeal arch mesenchyme at E9.5, as well as in presumptive cardiac neural crest cells in close proximity to outflow tract

cardiovascular system

abnormal heart morphology ( J:109474 )

• phenotype is stated to be identical to that of Fgf8^tm1.3Mrt/ Fgf8^tm1.4Mrt; Nkx2-5^tm1(cre)Rjs/ Nkx2-5⁺ mutants; however no data are presented

abnormal heart development ( J:109474 )

• anterior heart field (AHF) cells are mildly reduced compared to controls, resulting in thinning of splanchnic mesoderm (SM) layers

• at E9.5 cell proliferation in SM is reduced with cell mitotic indices decreased by 50% relative to controls; excessive cell death is detected from E8.5-9.5 in SM immediately distal to emerging outflow tract and in endoderm adjacent to the SM, with excessive cell death expanding into ventral pharyngeal endoderm by E9.5 but not in SM at this stage

craniofacial

abnormal pharyngeal arch morphology ( J:109474 )

• at E9.5 cell proliferation in pharyngeal endoderm is reduced with cell mitotic indices decreased by 60% relative to controls

abnormal pharyngeal arch mesenchyme morphology ( J:109474 )

• excessive neural crest cell death is observed in pharyngeal arch mesenchyme at E9.5

cellular

decreased mitotic index ( J:109474 )

• indices are reduced by 50% and 60% in splanchnic mesoderm and pharyngeal endoderm at E9.5

nervous system

abnormal neural crest cell morphology ( J:109474 )

• excessive neural crest cell death is observed in pharyngeal arch mesenchyme at E9.5, as well as in presumptive cardiac neural crest cells in close proximity to outflow tract

growth/size/body

abnormal pharyngeal arch mesenchyme morphology ( J:109474 )

• excessive neural crest cell death is observed in pharyngeal arch mesenchyme at E9.5

Genotype
MGI:5575766

cn5

• Allelic Composition: Dicer1^tm1Bdh/Dicer1^tm1Bdh; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129 * 129S7/SvEvBrd * C57BL/6

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:211548 )

• embryos die by E12.5

cardiovascular system

abnormal myocardium layer morphology ( J:211548 )

• poorly developed

pericardial edema ( J:211548 )

• by E12.5

abnormal cardiovascular system physiology ( J:211548 )

• embryos die at E12.5 from cardiac failure

homeostasis/metabolism

pericardial edema ( J:211548 )

• by E12.5

muscle

abnormal myocardium layer morphology ( J:211548 )

• poorly developed

Genotype
MGI:5532942

cn6

• Allelic Composition: Atoh8^tm1.1Mlkn/Atoh8^tm1.1Mlkn; Gata4^tm1.1Sad/Gata4⁺; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129 * C57BL/6

mortality/aging

mortality/aging ( J:203454 )

N • viable and present at the expected Mendelian ratio at P1

Genotype
MGI:4829788

cn7

• Allelic Composition: Foxp1^tm2.1Eem/Foxp1^tm2.1Eem; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129 * C57BL/6 * SJL

mortality/aging

neonatal lethality, complete penetrance ( J:163662 )

cardiovascular system

abnormal heart development ( J:163662 )

• expression analysis in cardiomyocytes indicates disruption of sarcomere structure and an inhibition of cardiomyocyte maturation

double outlet right ventricle ( J:163662 )

• at E14.5

thick interventricular septum ( J:163662 )

• by E16.5

ventricular septal defect ( J:163662 )

• at E14.5 ventricular septal defects are present; however, by E16.5 most mice do not have septal defects suggesting a delay in septal development

thick ventricular wall ( J:163662 )

• by E16.5 both the right and left ventricle walls are thicker compared to controls

increased fetal cardiomyocyte proliferation ( J:163662 )

• increased proliferation that is most prominent in the trabecular layer at E14.5 and E16.5

muscle

increased fetal cardiomyocyte proliferation ( J:163662 )

• increased proliferation that is most prominent in the trabecular layer at E14.5 and E16.5

abnormal sarcomere morphology ( J:163662 )

• expression analysis in cardiomyocytes indicates disruption of sarcomere structure

cellular

increased fetal cardiomyocyte proliferation ( J:163662 )

• increased proliferation that is most prominent in the trabecular layer at E14.5 and E16.5

Genotype
MGI:3818077

cn8

• Allelic Composition: Fgf8^tm1.3Mrt/Fgf8^tm1.4Mrt; Gt(ROSA)26Sor^tm1Sor/Gt(ROSA)26Sor^tm1Sor; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJaeSor * 129S7/SvEvBrd

cardiovascular system

abnormal heart development ( J:109474 )

• anterior heart field (AHF) cells are lost compared to controls; numbers of B-gal +ve cells in splanchnic mesoderm (SM) and pharyngeal endoderm are significantly reduced, causing thinning of these cell layers

• number of positive cells in pharyngeal arch core mesoderm (CM) is significantly decreased also

embryo

abnormal splanchnic mesoderm morphology ( J:109474 )

• thinning of splanchnic mesoderm due to significantly reduced numbers of B-gal +ve cells

Genotype
MGI:5707467

cn9

• Allelic Composition: Hic2^{Gt(E225A08)1.1Wrst}/Hic2^{Gt(E225A08)1.1Wrst}; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd

mortality/aging

mortality/aging ( J:225226 )

N • no embryonic lethality to E15.5

embryo

embryonic growth retardation ( J:225226 )

• 19% with mild developmental delay and hemorrhage

cardiovascular system

thin myocardium ( J:225226 )

• in 40% of mice

overriding aortic valve ( J:225226 )

• in 80% of mice

ventricular septal defect ( J:225226 )

• 80% with ventricular septal defects

hemorrhage ( J:225226 )

• in mice showing developmental delay

growth/size/body

embryonic growth retardation ( J:225226 )

• 19% with mild developmental delay and hemorrhage

muscle

thin myocardium ( J:225226 )

• in 40% of mice

Genotype
MGI:3818072

cn10

• Allelic Composition: Fgf8^tm1.3Mrt/Fgf8^tm1.4Mrt; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:109474 )

• mutant embryos are present at expected ratio up to E9.5, but a marked reduction is observed at later times with no surviving mutants by E10.5

embryo

pharyngeal arch hypoplasia ( J:109474 )

• arches are hypoplastic at E9.5

cardiovascular system

absent cardiac outflow tract ( J:109474 )

• presumptive outflow tract (OT) is almost completely absent at E9.5; only a small segment of myocardium joins left ventricle to aortic sac

abnormal heart tube morphology ( J:109474 )

• at E9.5, heart tube is severely truncated

dilated heart atrium ( J:109474 )

• both atria are slightly dilated at E9.5

dilated heart left ventricle ( J:109474 )

• slightly at E9.5

absent heart right ventricle ( J:109474 )

• almost completely absent at E9.5

craniofacial

pharyngeal arch hypoplasia ( J:109474 )

• arches are hypoplastic at E9.5

Genotype
MGI:5811817

cn11

• Allelic Composition: Casz1^tm1.1Flc/Casz1⁺; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * C57BL/6J * SJL

normal phenotype

no abnormal phenotype detected ( J:221324 )

• mice are viable, fertile and show no obvious phenotypic abnormalities

Genotype
MGI:5811822

cn12

• Allelic Composition: Casz1^tm1.1Flc/Casz1^tm1.1Flc; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * C57BL/6J * SJL

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:221324 )

• no viable embryos are identified after E14.5

• however, embryos appear grossly normal at E12.5

homeostasis/metabolism

edema ( J:221324 )

• severe edema at E13.5

cardiovascular system

thin myocardium ( J:221324 )

• severe thinning of the myocardium by E12.5

abnormal heart development ( J:221324 )

• abnormal heart development between E10.5 and E12.5

decreased fetal cardiomyocyte number ( J:221324 )

• at E12.5, the number of tropomyosin (TMY)-positive cardiomyocytes is significantly reduced in the ventricles

• however, no increase in programmed cell death is observed and actin filaments are intact

abnormal heart apex morphology ( J:221324 )

• heart fails to form an apex for either the left or the right ventricle

increased heart right atrium size ( J:221324 )

• enlarged right atrium at E12.5; more pronounced at E13.5

dilated heart right atrium ( J:221324 )

• ballooning of the right atria by E13.5, indicating blood pooling in the right ventricle

abnormal heart shape ( J:221324 )

• misshapen heart at E13.5

heart hypoplasia ( J:221324 )

• severe cardiac hypoplasia by E13.5

• at E12.5, cardiac hypoplasia is specific to cardiomyocytes and does not affect the epicardium or endothelial cells

abnormal heart ventricle morphology ( J:221324 )

• narrower ventricular lumens by E13.5

trabecula carnea hypoplasia ( J:221324 )

• decreased trabeculation at E12.5

abnormal interventricular septum morphology ( J:221324 )

• underdeveloped interventricular septum at E12.5

perimembraneous ventricular septal defect ( J:221324 )

• membranous ventricular septal defects by E13.5

abnormal heart left ventricle morphology ( J:221324 )

• malformed left ventricle at E12.5; more pronounced at E13.5

thin ventricular wall ( J:221324 )

• thinning of the ventricular walls starting at E12.5

distended pericardium ( J:221324 )

• inflated pericardial sacs at E13.5

hemorrhage ( J:221324 )

• severe blood hemorrhaging at E13.5

poor circulation ( J:221324 )

• decreased blood flow throughout the vasculature by E13.5

abnormal fetal cardiomyocyte physiology ( J:221324 )

• at E12.5, the G1-to-S phase progression of cardiomyocytes is impaired, as shown by a prolonged or arrested G1 phase, a reduction in DNA synthesis, an increase in phospho-RB, and a decrease in the cardiac mitotic index

decreased fetal cardiomyocyte proliferation ( J:221324 )

• cardiomyocyte proliferation is significantly reduced in E12.5 ventricles, as shown by EdU incorporation

cellular

decreased fetal cardiomyocyte proliferation ( J:221324 )

• cardiomyocyte proliferation is significantly reduced in E12.5 ventricles, as shown by EdU incorporation

abnormal cell cycle checkpoint function ( J:221324 )

• at E12.5, cell cycle profiling of cardiac nuclei revealed a significant increase of cells in G1 phase and a simultaneous decrease of cells in S phase, with no alteration in the % of cells in G2 phase

decreased mitotic index ( J:221324 )

• cardiomyocyte mitotic index is significantly reduced in E12.5 ventricles, as shown by phospho-histone H3 staining

muscle

trabecula carnea hypoplasia ( J:221324 )

• decreased trabeculation at E12.5

thin myocardium ( J:221324 )

• severe thinning of the myocardium by E12.5

decreased fetal cardiomyocyte proliferation ( J:221324 )

• cardiomyocyte proliferation is significantly reduced in E12.5 ventricles, as shown by EdU incorporation

Genotype
MGI:4880768

cn13

• Allelic Composition: Daam1^{Gt(RRT390)Byg}/Daam1^{Gt(RRT390)Byg}; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6J

mortality/aging

mortality/aging ( J:167714 )

N • cre mediated reversion rescues the lethality seen in homozygous mutants lacking cre expression in the heart

cardiovascular system

cardiovascular system phenotype ( J:167714 )

N • cre mediated reversion rescues cardiac defects seen in homozygous mutants lacking cre expression in the heart

embryo

decreased embryo size ( J:167714 )

• most embryos are smaller than wild-type littermates

growth/size/body

decreased embryo size ( J:167714 )

• most embryos are smaller than wild-type littermates

decreased body size ( J:167714 )

• most pups are smaller than wild-type littermates

Genotype
MGI:6150944

cn14

• Allelic Composition: Daam1^tm1.1Tpy/Daam1^tm1.1Tpy; Gt(ROSA)26Sor^tm1Sor/Gt(ROSA)26Sor⁺; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJaeSor * 129S7/SvEvBrd

muscle

abnormal cardiac muscle tissue morphology ( J:228507 )

• in E13.5 embryos

• cardiomyocytes smaller, rounded and loosely attached to each other with thin cellular projections in conotruncal regions

• absent thick protrusions from leading edges of cardiomyocytes invading non-myocardial tissue

• cardiomyocytes randomly distributed and mixed with endocardial cells at bases of blood vessels

cardiovascular system

abnormal cardiac muscle tissue morphology ( J:228507 )

• in E13.5 embryos

• cardiomyocytes smaller, rounded and loosely attached to each other with thin cellular projections in conotruncal regions

• absent thick protrusions from leading edges of cardiomyocytes invading non-myocardial tissue

• cardiomyocytes randomly distributed and mixed with endocardial cells at bases of blood vessels

Genotype
MGI:5907122

cn15

• Allelic Composition: Prox1^tm2Gco/Prox1^tm2Gco; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd

growth/size/body

enlarged heart ( J:212185 )

• cardiomegaly at 12 weeks of age

mortality/aging

premature death ( J:212185 )

• in mice that survive postnatally, lethality becomes fully penetrant between 7 and 14 weeks

postnatal lethality, incomplete penetrance ( J:212185 )

• about half the expected number of mutants are seen at P10

cardiovascular system

abnormal heart morphology ( J:212185 )

• fast-twitch skeletal muscle gene expression is elevated in hearts

abnormal myocardial fiber morphology ( J:212185 )

• myofibrillar disarray

thin myocardium ( J:212185 )

• myocardial thinning at late stages

thick tricuspid valve cusps ( J:212185 )

• thickening of the tricuspid valve leaflets

abnormal interventricular septum morphology ( J:212185 )

• mild ventricular septal defects

interventricular septum membranous part aneurysm ( J:212185 )

• the membranous portion of the ventricular septum is aneurysmal

abnormal interventricular septum muscular part morphology ( J:212185 )

• 20% of hearts show imperfections in the muscular ventricular septum

enlarged heart ( J:212185 )

• cardiomegaly at 12 weeks of age

dilated heart ( J:212185 )

• chamber dilation in both the atria and ventricles, with severity of dilation increasing with age to eventually affect all cardiac chambers

dilated cardiomyopathy ( J:212185 )

• between 8 and 14 weeks of age, all hearts are characterized by cardiac enlargement, chamber dilation, ventricular wall thinning, cardiac stress marker activation, and systolic dysfunction

• however, no obvious concentric cardiomyocyte hypertrophy is seen

decreased cardiac muscle contractility ( J:212185 )

• dilated and poorly contracting ventricles at 6 weeks of age, with mean left ventricular ejection fraction less than 30%

homeostasis/metabolism

abnormal cardiac thrombosis ( J:212185 )

• mice develop large intra-atrial and intraventricular thrombi at 12 weeks of age, indicating hemostasis associated with poor systolic function

• thrombi are seen as early as 8 weeks of age

abnormal atrial thrombosis ( J:212185 )

• large intra-atrial thrombi at 12 weeks of age

abnormal ventricular thrombosis ( J:212185 )

• large intraventricular thrombi at 12 weeks of age

muscle

abnormal myocardial fiber morphology ( J:212185 )

• myofibrillar disarray

thin myocardium ( J:212185 )

• myocardial thinning at late stages

dilated cardiomyopathy ( J:212185 )

• between 8 and 14 weeks of age, all hearts are characterized by cardiac enlargement, chamber dilation, ventricular wall thinning, cardiac stress marker activation, and systolic dysfunction

• however, no obvious concentric cardiomyocyte hypertrophy is seen

decreased cardiac muscle contractility ( J:212185 )

• dilated and poorly contracting ventricles at 6 weeks of age, with mean left ventricular ejection fraction less than 30%

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:212185

Genotype
MGI:6151066

cn16

• Allelic Composition: Daam1^tm1.1Tpy/Daam1^tm1.1Tpy; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺; Wnt5a^tm1Amc/Wnt5a⁺
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd

cardiovascular system

abnormal myocardial trabeculae morphology ( J:228507 )

• thicker right ventricular trabecular zones, extending into lumen in E16.5 embryos

thick myocardium compact layer ( J:228507 )

• in right ventricle of E16.5 embryos

muscle

abnormal myocardial trabeculae morphology ( J:228507 )

• thicker right ventricular trabecular zones, extending into lumen in E16.5 embryos

thick myocardium compact layer ( J:228507 )

• in right ventricle of E16.5 embryos

Genotype
MGI:6150926

cn17

• Allelic Composition: Daam1^tm1.1Tpy/Daam1^tm1.1Tpy; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺; Wnt5a^tm1Amc/Wnt5a^tm1Amc
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd

cardiovascular system

abnormal heart morphology ( J:228507 )

• right ventricle shifted anterior to left ventricle in E12.5 embryos

• AV cushion atop single ventricle connected to both atria in some embryos in E12.5 embryos

abnormal myocardial trabeculae morphology ( J:228507 )

• rudimentary in left ventricle of E16.5 embryos

abnormal myocardium compact layer morphology ( J:228507 )

• rudimentary in left ventricle of E16.5 embryos

abnormal interventricular septum morphology ( J:228507 )

• shorter than controls, not extended to the endocardial cushion in the atrioventricular canal in E12.5 embryos

abnormal heart right ventricle morphology ( J:228507 )

• mesenchyme-like organization of cardiomyocytes at ventricle base in E12.5 embryos

• right ventricle shifted anterior to left ventricle in E12.5 embryos

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:228507 )

• very few embryos seen at E16.5 and those that are, are mostly necrotic

muscle

abnormal myocardial trabeculae morphology ( J:228507 )

• rudimentary in left ventricle of E16.5 embryos

abnormal myocardium compact layer morphology ( J:228507 )

• rudimentary in left ventricle of E16.5 embryos

Genotype
MGI:6150919

cn18

• Allelic Composition: Daam1^tm1.1Tpy/Daam1^tm1.1Tpy; Daam2^tm1Tpy/Daam2^tm1Tpy; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd

cardiovascular system

cardiovascular system phenotype ( J:228507 )

N • compact layer width in E17.5 embryos

abnormal myocardial fiber morphology ( J:228507 )

• in 2-months old mice

• disturbed A-band marker Actc1 striation pattern

• nearly absent intermediate filament Desmin striation

• shorter A-bands

• Z-bands faint or absent

• no apparent I-bands, H-bands or M-lines

• intersecting and disorganized thick fibers in severely affected areas

abnormal intercalated disk morphology ( J:228507 )

• lower-density material frequently observed between membranes of adjacent cardiomyocytes in 2-months old mice through electron microscopy

abnormal myocardial trabeculae morphology ( J:228507 )

• in E17.5 embryos

• failure of trabeculae to assimilate into compact zone, resulting in occluded ventricular lumens

• wider trabecular layers

• thicker individual trabeculae

• inter-trabecular spaces filled with detached endothelial cells

heart hypoplasia ( J:228507 )

• in 2-months old mice

abnormal heart left ventricle morphology ( J:228507 )

• in 2-months old mice

• thicker walls and septa

• smaller lumen

abnormal heart right ventricle morphology ( J:228507 )

• in 2-months old mice

• thicker walls and septa

• smaller lumen

decreased left ventricle systolic pressure ( J:228507 )

• in 2-months old mice

• lower ejection fraction

• reduced fractional shortening

decreased right ventricle systolic pressure ( J:228507 )

• in 2-months old mice

• acceleration of pulmonary artery (PA) flow

• reduced fractional shortening

abnormal myocardial fiber physiology ( J:228507 )

• increased cardiomyocyte proliferation

muscle

abnormal myocardial fiber morphology ( J:228507 )

• in 2-months old mice

• disturbed A-band marker Actc1 striation pattern

• nearly absent intermediate filament Desmin striation

• shorter A-bands

• Z-bands faint or absent

• no apparent I-bands, H-bands or M-lines

• intersecting and disorganized thick fibers in severely affected areas

abnormal intercalated disk morphology ( J:228507 )

• lower-density material frequently observed between membranes of adjacent cardiomyocytes in 2-months old mice through electron microscopy

abnormal myocardial trabeculae morphology ( J:228507 )

• in E17.5 embryos

• failure of trabeculae to assimilate into compact zone, resulting in occluded ventricular lumens

• wider trabecular layers

• thicker individual trabeculae

• inter-trabecular spaces filled with detached endothelial cells

abnormal A band morphology ( J:228507 )

• disturbed A-band marker Actc1 striation pattern and shorter A-bands in cardiomyocytes of 2-months old mice

abnormal H zone morphology ( J:228507 )

• no apparent H-bands in cardiomyocytes of 2-months old mice

absent M line ( J:228507 )

• no apparent M lines in cardiomyocytes of 2-months old mice

abnormal I band morphology ( J:228507 )

• no apparent I-bands in cardiomyocytes of 2-months old mice

absent Z line ( J:228507 )

• in cardiomyocytes of some 2-months old mice

diffuse Z line ( J:228507 )

• in cardiomyocytes of some 2-months old mice

Genotype
MGI:6150918

cn19

• Allelic Composition: Daam1^tm1.1Tpy/Daam1^tm1.1Tpy; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd

cardiovascular system

cardiovascular system phenotype ( J:228507 )

N • pulmonary artery and aorta in E16.5 embryos

abnormal myocardial trabeculae morphology ( J:228507 )

• in E16.5 embryos

• thicker ventricular trabecular zones, extending into lumen

• inconsistent size of right ventricular trabeculae

• irregular spacing of right ventricular trabeculae

• disorganized left ventricular trabeculae

• left ventricular trabeculae occupy much of ventricular lumen

thin ventricle myocardium compact layer ( J:228507 )

• in E16.5 embryos

abnormal heart left ventricle morphology ( J:228507 )

• in E16.5 embryos

• disorganized

• occupy much of lumen

• thicker trabecular zones

• thinner compact zones

abnormal heart right ventricle morphology ( J:228507 )

• in E16.5 embryos

• free wall does not extend as close to heart apex of 8-months old mice as in control mice

• base closer to tricuspid valve than in controls

• base not aligned with base of left ventricle

• thicker trabecular zones

• thinner compact zones

• inconsistent size of trabeculae

• irregular spacing of trabeculae

abnormal diastolic filling velocity ( J:228507 )

• mean E/A ratio (flow velocity across mitral valve early in diastole divided by that late in diastole) in left ventricle of 2-months old mice is less than 1 in 8-months old mice, compared to greater than 1 in control mice

decreased right ventricle systolic pressure ( J:228507 )

• in 8-months old mice

• lower acceleration of pulmonary artery (PA) flow, indicating reduced RV contraction force

• reduced fractional shortening

abnormal pulmonary pressure ( J:228507 )

• lower acceleration of pulmonary artery (PA) flow in 8-months old mice

muscle

abnormal myocardial trabeculae morphology ( J:228507 )

• disorganized left ventricular trabeculae

• in E16.5 embryos

• thicker ventricular trabecular zones, extending into lumen

• inconsistent size of right ventricular trabeculae

• irregular spacing of right ventricular trabeculae

• left ventricular trabeculae occupy much of ventricular lumen

thin ventricle myocardium compact layer ( J:228507 )

• in E16.5 embryos

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
intrinsic cardiomyopathy		DOID:0060036		J:228507

Genotype
MGI:3851399

cn20

• Allelic Composition: Zfpm2^tm1Sho/Zfpm2^tm2Sho; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd

Abnormal heart development and coronary vasculogenesis in Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺ Zfpm2^tm1Sho/Zfpm2^tm2Sho mice

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:150452 )

• embryos die by E13.5-E14.5

cardiovascular system

thin myocardium compact layer ( J:150452 )

• compact myocardium is thin

abnormal atrioventricular cushion morphology ( J:150452 )

• atrio-ventricular cushion defect is observed

abnormal coronary vessel morphology ( J:150452 )

• coronary vascular plexus is significantly decreased compared to controls; myocardium contains few coronary vessels

overriding aortic valve ( J:150452 )

atrial septal defect ( J:150452 )

• large atrial septal defect is observed in embryos

ventricular septal defect ( J:150452 )

• large ventricular septal defect is observed

pericardial effusion ( J:150452 )

• embryos display pericardial effusion prior to death

hemorrhage ( J:150452 )

• embryos display hemorrhage prior to death

homeostasis/metabolism

pericardial effusion ( J:150452 )

• embryos display pericardial effusion prior to death

skin edema ( J:150452 )

• embryos develop subcutaneous edema prior to death

integument

skin edema ( J:150452 )

• embryos develop subcutaneous edema prior to death

muscle

thin myocardium compact layer ( J:150452 )

• compact myocardium is thin

Genotype
MGI:4843919

cn21

• Allelic Composition: Shh^tm1Chg/Shh^tm2Amc; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ

cardiovascular system

abnormal artery morphology ( J:135134 )

• at E10.5 and E18.5, mice exhibit abnormal arch-artery patterning compared to in wild-type mice

abnormal cardiac outflow tract development ( J:135134 )

• at E10.5, mice exhibit short outflow tract compared with wild-type mice

• mice exhibit cell death in the anterior heart field unlike in wild-type mice

persistent truncus arteriosus ( J:135134 )

• at E18.5

embryo

abnormal neural crest cell apoptosis ( J:135134 )

• mice exhibit cell death in neural crest cells unlike in wild-type mice

abnormal neural crest cell migration ( J:135134 )

• mice exhibit abnormal neural crest cells localization and septation defects compared with wild-type mice

cellular

abnormal neural crest cell apoptosis ( J:135134 )

• mice exhibit cell death in neural crest cells unlike in wild-type mice

abnormal neural crest cell migration ( J:135134 )

• mice exhibit abnormal neural crest cells localization and septation defects compared with wild-type mice

Genotype
MGI:6159009

cn22

• Allelic Composition: Hspb7^tm1.1Chen/Hspb7^tm1.1Chen; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ * C57BL/6

General and heart phenotype of Hspb7^tm1.1Chen/Hspb7^tm1.1Chen Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺ mice

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:256653 )

• most embryos died by E12.5, with no live embryos recovered at E13.5, similar to Hspb7^tm1.2Chen homozygotes

cardiovascular system

abnormal heart morphology ( J:256653 )

• overall heart phenotype is stated to be similar to that observed in Hspb7^tm1.2Chen homozygotes

Genotype
MGI:3783262

cn23

• Allelic Composition: Gata4^tm1.1Sad/Gata4^tm1.1Sad; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CD-1

mortality/aging

prenatal lethality, complete penetrance ( J:121367 )

• animals die between E12.5 and E15.5

cardiovascular system

thin ventricular wall ( J:121367 )

• uniform reduction in ventricular wall thickness is observed in embryos

increased cardiomyocyte apoptosis ( J:121367 )

• higher levels of apoptosis (TUNEL) are observed compared to Myh6-cre; Gata4-conditional mutants

muscle

increased cardiomyocyte apoptosis ( J:121367 )

• higher levels of apoptosis (TUNEL) are observed compared to Myh6-cre; Gata4-conditional mutants

cellular

increased cardiomyocyte apoptosis ( J:121367 )

• higher levels of apoptosis (TUNEL) are observed compared to Myh6-cre; Gata4-conditional mutants

Genotype
MGI:3620974

cn24

• Allelic Composition: Bmp2^tm1Jfm/Bmp2^tm1Jfm; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129S4/SvJaeSor

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:104417 )

• although present at the expected Mendelian frequency at E9.5, all mutant embryos exhibit heart failure at E10.5

cardiovascular system

abnormal myocardium layer morphology ( J:104417 )

• by E10.5, mutant embryos exhibit a severely compromised myocardium

abnormal cardiac epithelial to mesenchymal transition ( J:104417 )

• at E9.5, all mutant embryos, including those with cardiac jelly deposition, fail to undergo epithelial to mesenchymal transition (EMT) in the forming AV endocardial cushions

abnormal cardiac jelly morphology ( J:104417 )

• at E9.5, 43% of mutants fail to expand the space between the myocardium and the endocardium, indicating defective cardiac jelly formation

abnormal fetal atrioventricular canal morphology ( J:104417 )

• at E9.5, mutant embryos display abnormal AV canal constriction

pericardial effusion ( J:104417 )

• by E10.5, all mutant embryos exhibit pericardial effusion

growth/size/body

embryonic growth retardation ( J:104417 )

• by E10.5, all mutant embryos appear growth retarded

embryo

embryonic growth retardation ( J:104417 )

• by E10.5, all mutant embryos appear growth retarded

homeostasis/metabolism

pericardial effusion ( J:104417 )

• by E10.5, all mutant embryos exhibit pericardial effusion

muscle

abnormal myocardium layer morphology ( J:104417 )

• by E10.5, mutant embryos exhibit a severely compromised myocardium

Genotype
MGI:3043044

cn25

• Allelic Composition: Bmp4^tm1Jfm/Bmp4^tm1.1Jfm; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129S4/SvJaeSor * 129S7/SvEvBrd

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:89237 )

• most mice died by E13.5, although an occasional fetus survived to E18.5, putatively due to variability in the expression of cre recombinase

• peripheral edema that was often associated with pericardial effusion indicated that lethality was secondary to heart failure

cardiovascular system

abnormal pharyngeal arch artery morphology ( J:89237 )

• severe defects in the architecture of the brancial arch artery due to impaired remodeling

• variable branching and abnormal regression and remodeling

abnormal pulmonary artery morphology ( J:89237 )

• only one pulmonary artery originates from the ductus arteriosis and the fate of the second pulmonary artery is not clear

aortopulmonary window ( J:89237 )

• majority exhibited a proximal aortopulmonary window, in which the proximal aspect of the outflow tract septum failed to form

abnormal aortic arch and aortic arch branch attachment ( J:89237 )

• the left carotid artery branched either from the right brachiocephalic artery in the most severely affected embryos or directly from the aorta in more mildly affected embryos

interrupted aortic arch, type b ( J:89237 )

• interruption (type B) of the aorta between the left carotid and the left subclavian arteries

persistent truncus arteriosus ( J:89237 )

abnormal heart development ( J:89237 )

abnormal conotruncal ridge morphology ( J:89237 )

• growth was delayed and the cushions were hypoplastic

• cell proliferation is reduced in the cushion mesenchyme, relative to wild-type

conotruncal ridge hypoplasia ( J:89237 )

perimembraneous ventricular septal defect ( J:89237 )

• observed in all examined fetuses

• putatively due to a defect in the conotruncal mesenchyme

semilunar valve hypoplasia ( J:89237 )

• hypoplastic semilunar valves

pericardial effusion ( J:89237 )

• peripheral edema that was often associated with pericardial effusion

homeostasis/metabolism

pericardial effusion ( J:89237 )

• peripheral edema that was often associated with pericardial effusion

hydrops fetalis ( J:89237 )

• peripheral edema that was often associated with pericardial effusion

craniofacial

abnormal pharyngeal arch artery morphology ( J:89237 )

• severe defects in the architecture of the brancial arch artery due to impaired remodeling

• variable branching and abnormal regression and remodeling

embryo

abnormal pharyngeal arch artery morphology ( J:89237 )

• severe defects in the architecture of the brancial arch artery due to impaired remodeling

• variable branching and abnormal regression and remodeling

Genotype
MGI:3763210

cn26

• Allelic Composition: Grk2^tm1Gwd/Grk2^tm1Gwd; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129S4/SvJaeSor * 129S7/SvEvBrd * C57BL/6

mortality/aging

mortality/aging ( J:126501 )

N • unlike in Adrbk1^tm1.1Gwd homozygotes, mice survive into adulthood

homeostasis/metabolism

decreased physiological sensitivity to xenobiotic ( J:126501 )

• inotropic and lusitropic tachyphylaxis effects induced by isoproterenol are blunted

increased physiological sensitivity to xenobiotic ( J:126501 )

• mice exhibit a leftward shift of the peak +dP/dt response to infused doses of isoproterenol with an EC50 of 0.4+/-0.1 ng/g per minute compared to 0.7+/-0.04 ng/g per minute in Adrbk1^tm1Gwd control mice

• when exposed to 30 mg/kg per day isoproterenol, mice develop adverse cardiac remodeling (decreased heart rate, wall thickness to chamber radius ratio) and decreased contractile performance with generalized interstitial and replacement fibrosis in addition to the cardiac dilation and increased left ventricle mass observed in similarly treated Adrbk1^tm1Gwd control mice

cardiovascular system

cardiovascular system phenotype ( J:126501 )

N • unlike in Adrbk1^tm1.1Gwd homozygotes, heart development is normal

Genotype
MGI:5470169

cn27

• Allelic Composition: Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺; Zic3^tm2.1Jwb/Y
• Genetic Background: involves: 129S4/SvJaeSor * 129S7/SvEvBrd * C57BL/6J

normal phenotype

no abnormal phenotype detected ( J:192577 )

♂ • mice are indistinguishable from control mice with normal survival and heart development

Genotype
MGI:3851408

cn28

• Allelic Composition: Gata4^tm1Sho/Gata4^tm1.1Wtp; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129S6/SvEvTac * 129S7/SvEvBrd

Edema, peripheral hemorrhage, and reduced coronary plexus in Gata4^tm1.1Wtp/Gata4^tm1Sho Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺ embryos and enlarged dilated ventricles and increased fibrosis in Gata4^tm1.1Wtp/Gata4^tm1Sho Tg(Myh6-cre)2182Mds/0 hearts

cardiovascular system

thin myocardium compact layer ( J:150452 )

• compact myocardium is thin

abnormal atrioventricular cushion morphology ( J:150452 )

• atrio-ventricular cushion defect is observed

abnormal coronary vessel morphology ( J:150452 )

• coronary vascular development is impaired

ventricular septal defect ( J:150452 )

• ventricular septal defect is observed

hemorrhage ( J:150452 )

• peripheral hemorrhage is observed at E13.5

homeostasis/metabolism

skin edema ( J:150452 )

• observed at E13.5

integument

skin edema ( J:150452 )

• observed at E13.5

muscle

thin myocardium compact layer ( J:150452 )

• compact myocardium is thin

Genotype
MGI:3851410

cn29

• Allelic Composition: Gata4^tm1Sho/Gata4⁺; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129S6/SvEvTac * 129S7/SvEvBrd

cardiovascular system

cardiovascular system phenotype ( J:150452 )

N • animals show normal development

Genotype
MGI:5490242

cn30

• Allelic Composition: Fkbp1a^tm1.1Shou/Fkbp1a^tm1Zuk; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129S7/SvEvBrd

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:195489 )

• death occurs between E14.5 and birth

cardiovascular system

abnormal heart ventricle morphology ( J:195489 )

• mutants phenocopy Fkbp1a^tm1Zuk mice, showing hypertrabeculation, noncompaction, and ventral septal defects (VSDs) with complete penetrance

Genotype
MGI:3639276

cn31

• Allelic Composition: Gata4^tm1.1Wtp/Gata4^tm1.1Wtp; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129S7/SvEvBrd

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:99203 )

• lethality by E11.5

cardiovascular system

abnormal cardiac epithelial to mesenchymal transition ( J:99203 )

• defect in the EMT of endocardial cells that normally generates cushion mesenchyme

conotruncal ridge hypoplasia ( J:99203 )

• the outflow tract endocardial cushions are small and contain few mesenchymal cells

atrioventricular cushion hypoplasia ( J:99203 )

• the atrioventricular endocardial cushions are small and contain few mesenchymal cells

common ventricle ( J:99203 )

• 15 of 21 embryos at E9.5 display a single predominant ventricular chamber that connects to an outflow tract located toward the rostral side of the chamber; the predominant ventricular chamber is the left ventricle

heart hypoplasia ( J:99203 )

• all embryos display marked myocardial hypoplasia, affecting both the compact and trabecular myocardium

heart right ventricle hypoplasia ( J:99203 )

• 6 of 21 embryos at E9.5 have a normal to mildy hypoplastic right ventricle, rest have severe right ventricle hypoplasia

pericardial effusion ( J:99203 )

• by E10.5, have large pericardial effusions

abnormal fetal cardiomyocyte proliferation ( J:99203 )

• cardiomyocyte proliferation is more severely reduced in the right ventricle than in the left ventricle

embryo

embryonic growth retardation ( J:99203 )

• by E10.5, embryos are mildly delayed in overall development

muscle

abnormal fetal cardiomyocyte proliferation ( J:99203 )

• cardiomyocyte proliferation is more severely reduced in the right ventricle than in the left ventricle

growth/size/body

embryonic growth retardation ( J:99203 )

• by E10.5, embryos are mildly delayed in overall development

homeostasis/metabolism

pericardial effusion ( J:99203 )

• by E10.5, have large pericardial effusions

cellular

abnormal fetal cardiomyocyte proliferation ( J:99203 )

• cardiomyocyte proliferation is more severely reduced in the right ventricle than in the left ventricle

Genotype
MGI:5476840

cn32

• Allelic Composition: Zic3^tm1.1Smwa/Y; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129S7/SvEvBrd

normal phenotype

no abnormal phenotype detected ( J:194989 )

♂ • viable with no cardiac looping defects detected

Genotype
MGI:6766587

cn33

• Allelic Composition: Hand1^tm5Abfi/Hand1⁺; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129S7/SvEvBrd

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:311466 )

• no mutants are recovered beyond E15.5

cardiovascular system

abnormal myocardial trabeculae morphology ( J:311466 )

• hypotrabeculation

thin left ventricle myocardium compact layer ( J:311466 )

• left ventricle compact zone is thin

• however, left ventricle chamber size is proportional to right ventricle size and to controls

thin myocardium ( J:311466 )

• thin walled myocardium

abnormal cardiac outflow tract development ( J:311466 )

• elongated outflow tract; the outflow tracts extend farther into the forming right ventricle

abnormal interventricular septum morphology ( J:311466 )

• poorly formed interventricular septum that is positioned to the right of the endocardial cushions

ventricular septal defect ( J:311466 )

• E14.5 hearts exhibit ventricular septal defects both membranous and muscular in nature

decreased heart right ventricle size ( J:311466 )

• right ventricle appears smaller

hemorrhage ( J:311466 )

cellular

increased cell death ( J:311466 )

• hearts show increased cell death within the cardiac ventricles and the outflow tract

• however, cell proliferation is not altered

homeostasis/metabolism

cardiac edema ( J:311466 )

• the right ventricle shows signs of edema

muscle

abnormal myocardial trabeculae morphology ( J:311466 )

• hypotrabeculation

thin left ventricle myocardium compact layer ( J:311466 )

• left ventricle compact zone is thin

• however, left ventricle chamber size is proportional to right ventricle size and to controls

thin myocardium ( J:311466 )

• thin walled myocardium

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	hypoplastic left heart syndrome	DOID:9955	OMIM:241550 OMIM:614435	J:311466

Genotype
MGI:5543776

cn34

• Allelic Composition: Ehmt1^tm2Yshk/Ehmt1^tm2Yshk; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129S7/SvEvBrd

mortality/aging

premature death ( J:204470 )

• one mouse that survived to weaning died shortly after

neonatal lethality, incomplete penetrance ( J:204470 )

• despite being present at E18.5, only one mouse was found at weaning and died shortly after

• no dead mice are detected before weaning indicating neonatal lethality

cardiovascular system

decreased atrioventricular cushion size ( J:204470 )

abnormal mitral valve cusp morphology ( J:204470 )

• the anterior leaflet has an apparent cleft

absent tricuspid valve cusps ( J:204470 )

atrioventricular septal defect ( J:204470 )

Genotype
MGI:4843927

cn35

• Allelic Composition: Smo^tm2Amc/Smo^tm2.1Amc; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129S7/SvEvBrd * 129X1/SvJ

cardiovascular system

abnormal artery morphology ( J:135134 )

• at E10.5 and E18.5, mice exhibit abnormal arch-artery patterning compared to in wild-type mice

abnormal cardiac outflow tract development ( J:135134 )

• at E10.5, mice exhibit short outflow tract compared with wild-type mice

• mice exhibit cell death in the anterior heart field unlike in wild-type mice

persistent truncus arteriosus ( J:135134 )

• at E18.5

embryo

abnormal neural crest cell apoptosis ( J:135134 )

• mice exhibit cell death in neural crest cells unlike in wild-type mice

abnormal neural crest cell migration ( J:135134 )

• mice exhibit abnormal neural crest cells localization and septation defects compared with wild-type mice

cellular

abnormal neural crest cell apoptosis ( J:135134 )

• mice exhibit cell death in neural crest cells unlike in wild-type mice

abnormal neural crest cell migration ( J:135134 )

• mice exhibit abnormal neural crest cells localization and septation defects compared with wild-type mice

Genotype
MGI:3768916

cn36

• Allelic Composition: Frs2^tm1Fwan/Frs2^tm1Fwan; Nkx2-5^tm1(cre)Rjs/?
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

cardiovascular system

abnormal interventricular septum morphology ( J:128712 )

• newborn mice do not have a fully developed wall separating the ventricules

Genotype
MGI:3046805

cn37

• Allelic Composition: Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺; Tbx1^tm1Bld/Tbx1^tm3Bld
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

cardiovascular system

abnormal pharyngeal arch artery morphology ( J:91013 )

• the aortic arch abnormalities are milder than those present in Tbx1^tm1Bld homozygotes as the 3rd and 6th pharyngeal arch artery form and develop normally while the 4th pharyngeal arch artery is absent or hypoplastic

absent fourth pharyngeal arch artery ( J:91013 )

• the 4th pharyngeal arch artery is absent or hypoplastic

fourth pharyngeal arch artery hypoplasia ( J:91013 )

• the 4th pharyngeal arch artery is absent or hypoplastic

persistent truncus arteriosus ( J:91013 )

• the same cardiovascular phenotype as in Tbx1^tm1Bld homozygotes is seen including truncus arteriosus

cellular

decreased mitotic index ( J:91013 )

• the mitotic index in the secondary heart field and adjacent splanchnic mesoderm is reduced by 18% and 19%, respectively

craniofacial

craniofacial phenotype ( J:91013 )

N • none of the mutants had cleft palates at E18.5 unlike Tbx1^tm1Bld homozygotes

abnormal pharyngeal arch artery morphology ( J:91013 )

• the aortic arch abnormalities are milder than those present in Tbx1^tm1Bld homozygotes as the 3rd and 6th pharyngeal arch artery form and develop normally while the 4th pharyngeal arch artery is absent or hypoplastic

absent fourth pharyngeal arch artery ( J:91013 )

• the 4th pharyngeal arch artery is absent or hypoplastic

fourth pharyngeal arch artery hypoplasia ( J:91013 )

• the 4th pharyngeal arch artery is absent or hypoplastic

immune system

small thymus ( J:91013 )

• the thymus is present but smaller than normal with widely separated lobes

embryo

abnormal pharyngeal arch artery morphology ( J:91013 )

• the aortic arch abnormalities are milder than those present in Tbx1^tm1Bld homozygotes as the 3rd and 6th pharyngeal arch artery form and develop normally while the 4th pharyngeal arch artery is absent or hypoplastic

absent fourth pharyngeal arch artery ( J:91013 )

• the 4th pharyngeal arch artery is absent or hypoplastic

fourth pharyngeal arch artery hypoplasia ( J:91013 )

• the 4th pharyngeal arch artery is absent or hypoplastic

hematopoietic system

small thymus ( J:91013 )

• the thymus is present but smaller than normal with widely separated lobes

endocrine/exocrine glands

small thymus ( J:91013 )

• the thymus is present but smaller than normal with widely separated lobes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
DiGeorge syndrome		DOID:11198	OMIM:188400	J:91013

Genotype
MGI:5792841

cn38

• Allelic Composition: Gt(ROSA)26Sor^{tm1.1(CAG-Mirc20)Eem}/Gt(ROSA)26Sor⁺; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

mortality/aging

premature death ( J:233994 )

• mice die by P28

cardiovascular system

abnormal myocardial fiber morphology ( J:233994 )

• at P17, cardiomyocytes exhibit an increase in the percentage of mononucleated and binucleated cells with a decrease in the percentage of multinucleated cells compared with control cells

• disorganized sarcomeric structure at P20

decreased myocardial fiber size ( J:233994 )

• at P20

enlarged heart ( J:233994 )

• at P20

increased heart weight ( J:233994 )

• increased heart weight to tibia length ratio at P20

decreased cardiac muscle contractility ( J:233994 )

• reduced ejection fraction and fractional shortening

increased fetal cardiomyocyte proliferation ( J:233994 )

• at E18.5

abnormal myocardial fiber physiology ( J:233994 )

• increased cardiomyocytes proliferation in postnatal hearts

increased cardiomyocyte apoptosis ( J:233994 )

• at P20

cellular

increased fetal cardiomyocyte proliferation ( J:233994 )

• at E18.5

increased cardiomyocyte apoptosis ( J:233994 )

• at P20

muscle

abnormal myocardial fiber morphology ( J:233994 )

• at P17, cardiomyocytes exhibit an increase in the percentage of mononucleated and binucleated cells with a decrease in the percentage of multinucleated cells compared with control cells

• disorganized sarcomeric structure at P20

decreased myocardial fiber size ( J:233994 )

• at P20

decreased cardiac muscle contractility ( J:233994 )

• reduced ejection fraction and fractional shortening

increased fetal cardiomyocyte proliferation ( J:233994 )

• at E18.5

increased cardiomyocyte apoptosis ( J:233994 )

• at P20

growth/size/body

enlarged heart ( J:233994 )

• at P20

increased heart weight ( J:233994 )

• increased heart weight to tibia length ratio at P20

Genotype
MGI:6879488

cn39

• Allelic Composition: Foxc2^tm1.1Miu/Foxc2^tm1.1Miu; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * C57BL/6J * SJL

mortality/aging

neonatal lethality, complete penetrance ( J:316530 )

• all mice die soon after birth

cardiovascular system

interrupted aortic arch, type b ( J:316530 )

• at E18.5, seven of 12 embryos show an interrupted aortic arch type B (IAA-B), where part of the aortic arch between the left common carotid artery and the left subclavian artery is absent

• defect in aortic arch remodeling is clearly visible (as IAA-B) at E13.5, but not at E12.5, indicating that initial formation and patterning of pharyngeal arch arteries is normal

• however, embryos appear grossly normal and show spontaneous movements and cardiac pulsations at E14.5

perimembraneous ventricular septal defect ( J:316530 )

• at E18.5, five of 12 embryos show a VSD where membranous portions of the ventricular septum fail to fuse

craniofacial

craniofacial phenotype ( J:316530 )

N • newborn pups exhibit no apparent craniofacial defects

skeleton

skeleton phenotype ( J:316530 )

N • newborn pups exhibit no apparent skeletal defects

Genotype
MGI:5571466

cn40

• Allelic Composition: Adam17^tm1.1Wesh/Adam17^tm1.1Wesh; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * FVB/N

mortality/aging

mortality/aging ( J:210193 )

N • mice exhibit normal neonatal survival

cardiovascular system

abnormal myocardium layer morphology ( J:210193 )

• reduced myocardial compaction at E18.5

abnormal myocardial trabeculae morphology ( J:210193 )

• thickened at E18.5

thin myocardium ( J:210193 )

• at E18.5

enlarged heart ( J:210193 )

• at E18.5

muscle

abnormal myocardium layer morphology ( J:210193 )

• reduced myocardial compaction at E18.5

abnormal myocardial trabeculae morphology ( J:210193 )

• thickened at E18.5

thin myocardium ( J:210193 )

• at E18.5

growth/size/body

enlarged heart ( J:210193 )

• at E18.5

Genotype
MGI:5603566

cn41

• Allelic Composition: Akap6^tm1.1Mskf/Akap6^tm1.1Mskf; Nkx2-5^tm1(cre)Rjs/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * SJL

normal phenotype

no abnormal phenotype detected ( J:214288 )

• no overt phenotype is observed by 6 months of age

Genotype
MGI:5446510

cn42

• Allelic Composition: Yap1^tm1.1Eno/Yap1^tm1.1Eno; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129S/SvEv

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:189577 )

• embryos are dead at E10.5

cardiovascular system

abnormal myocardium layer morphology ( J:189577 )

thin myocardium ( J:189577 )

• abnormally thin myocardium

• ventricular myocyte number is significantly reduced

• cardiac looping and chamber formation are normal

decreased heart rate ( J:189577 )

• slower heart beat at E9.5

• mice are normal at E8.5

muscle

abnormal myocardium layer morphology ( J:189577 )

thin myocardium ( J:189577 )

• abnormally thin myocardium

• ventricular myocyte number is significantly reduced

• cardiac looping and chamber formation are normal

Genotype
MGI:7492254

cx43

• Allelic Composition: Nipbl^{Gt(RRS564)Byg}/Nipbl⁺; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * CD-1

cardiovascular system

abnormal heart morphology ( J:236978 )

• increased incidence of heart defects compared to mice heterozygous for the Nipbl allele alone (83% compared to 30%)

• spectrum of defects is more varied in type and more severe than in mice heterozygous for the Nipbl allele alone

persistent truncus arteriosus ( J:236978 )

• in 2 heartts

atrial septal defect ( J:236978 )

• sometimes seen in combination with ventricular septal defects

ventricular septal defect ( J:236978 )

• sometimes seen in combination with atrial septal defects

Genotype
MGI:3851519

cx44

• Allelic Composition: Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺; Nsd2^tm1Ykan/Nsd2⁺
• Genetic Background: involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6

cardiovascular system

abnormal interatrial septum morphology ( J:150360 )

• hypoplasia of the septum secundum was observed more frequently in E18.5 embryos than in controls

atrial septal defect ( J:150360 )

• one-third of E18.5 embryos have atrial septum defects

perimembraneous ventricular septal defect ( J:150360 )

• one-third of E18.5 embryos have membranous ventricular septum defects