Phenotypes associated with this allele

• Allele Symbol: Nkx2-5⁺
• Allele Name: wild type
• Allele ID: MGI:2153461
• Summary: 79 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Nkx2-5^tm1.1Krc/Nkx2-5^+	129S2.Cg(FVB)-Nkx2-5^tm1.1Krc	MGI:6314343
ht2	Nkx2-5^tm1.1Hkas/Nkx2-5^+	129S2.Cg-Nkx2-5^tm1.1Hkas	MGI:6294720
ht3	Nkx2-5^tm1.1Hkas/Nkx2-5^+	(129S2.Cg-Nkx2-5^tm1.1Hkas x C57BL/6)F1	MGI:6294743
ht4	Nkx2-5^tm2.1Mwc/Nkx2-5^+	B6J.Cg-Nkx2-5^tm2.1Mwc/Mwc	MGI:5829832
ht5	Nkx2-5^tm3.1Mwc/Nkx2-5^+	B6J.Cg-Nkx2-5^tm3.1Mwc/Mwc	MGI:5882084
ht6	Nkx2-5^tm4Rph/Nkx2-5^+	either: (involves: 129S1/Sv * 129T2/SvEms) or (involves: 129S1/Sv * C57BL/6J)	MGI:3655274
ht7	Nkx2-5^tm4Rph/Nkx2-5^+	either: (involves: 129S1/Sv * C57BL/6 * FVB/N) or (involves: 129S1/Sv * C57BL/6 * QS)	MGI:3655284
ht8	Nkx2-5^tm1Wehi/Nkx2-5^+	involves: 129P2/OlaHsd	MGI:5426985
ht9	Nkx2-5^tm1Wehi/Nkx2-5^+	involves: 129P2/OlaHsd * C57BL/6J * C57BL/10J	MGI:3655208
ht10	Nkx2-5^tm4Rph/Nkx2-5^+	involves: 129S1/Sv	MGI:3579848
ht11	Nkx2-5^tm1.1Burg/Nkx2-5^+	involves: 129S1/Sv * 129S2/SvPasCrl * 129X1/SvJ	MGI:6286233
ht12	Nkx2-5^tm2Siz/Nkx2-5^+	involves: 129S4/SvJaeSor	MGI:3041124
ht13	Nkx2-5^tm1Siz/Nkx2-5^+	involves: 129S4/SvJaeSor	MGI:3623792
cn14	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
cn15	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
cn16	Dicer1^tm1Bdh/Dicer1^tm1Bdh Nkx2-5^tm2(cre)Rph/Nkx2-5^+	involves: 129 * 129S1/Sv	MGI:7341797
cn17	Sox7^tm1.1Nat/Sox7^tm1.1Nat Nkx2-5^tm2(cre)Rph/Nkx2-5^+	involves: 129 * 129S1/Sv * C57BL/6 * SJL	MGI:7550409
cn18	Fgf8^tm1.3Mrt/Fgf8^tm2Mrt Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129 * 129S7/SvEvBrd	MGI:3818073
cn19	Bnip3l^tm1Gwd/Bnip3l^tm1Gwd Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129 * 129S7/SvEvBrd	MGI:4430398
cn20	Dicer1^tm1Bdh/Dicer1^tm1Bdh Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129 * 129S7/SvEvBrd * C57BL/6	MGI:5575766
cn21	Atoh8^tm1.1Mlkn/Atoh8^tm1.1Mlkn Gata4^tm1.1Sad/Gata4^+ Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129 * C57BL/6	MGI:5532942
cn22	Foxp1^tm2.1Eem/Foxp1^tm2.1Eem Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129 * C57BL/6 * SJL	MGI:4829788
cn23	Nkx2-5^tm2(cre)Rph/Nkx2-5^+ Pbx1^tm1.1Koss/Pbx1^tm1.1Koss	involves: 129P2/OlaHsd * 129S1/Sv	MGI:5426979
cn24	Pbx1^tm1Koss/Pbx1^tm1Koss Nkx2-5^tm2(cre)Rph/Nkx2-5^+	involves: 129P2/OlaHsd * 129S1/Sv	MGI:5426980
cn25	Cdkn2b^tm1Bbd/Cdkn2b^tm1Bbd Pbx1^tm1Koss/Pbx1^tm1Koss Nkx2-5^tm2(cre)Rph/Nkx2-5^+	involves: 129P2/OlaHsd * 129S1/Sv	MGI:5426986
cn26	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
cn27	Fgf8^tm1.3Mrt/Fgf8^tm1.4Mrt Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129P2/OlaHsd * 129S7/SvEvBrd	MGI:3818072
cn28	Hic2^Gt(E225A08)1.1Wrst/Hic2^Gt(E225A08)1.1Wrst Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129P2/OlaHsd * 129S7/SvEvBrd	MGI:5707467
cn29	Casz1^tm1.1Flc/Casz1^+ Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * C57BL/6J * SJL	MGI:5811817
cn30	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
cn31	Daam1^Gt(RRT390)Byg/Daam1^Gt(RRT390)Byg Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6J	MGI:4880768
cn32	Pbx1^tm1Koss/Pbx1^tm1Koss Pbx2^tm1Mlc/Pbx2^+ Nkx2-5^tm2(cre)Rph/Nkx2-5^+	involves: 129P2/OlaHsd * 129S/Sv * 129S1/Sv	MGI:5426982
cn33	Hccs^tm1Tcc/Hccs^tm1Tcc Nkx2-5^tm2(cre)Rph/Nkx2-5^+	involves: 129S1/Sv	MGI:3826965
cn34	Hccs^tm1Tcc/Y Nkx2-5^tm2(cre)Rph/Nkx2-5^+	involves: 129S1/Sv	MGI:3826966
cn35	Hccs^tm1Tcc/Hccs^+ Nkx2-5^tm2(cre)Rph/Nkx2-5^+	involves: 129S1/Sv	MGI:3826967
cn36	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
cn37	Gas2l3^tm1c(EUCOMM)Hmgu/Gas2l3^tm1c(EUCOMM)Hmgu Nkx2-5^tm2(cre)Rph/Nkx2-5^+	involves: 129S1/Sv * 129S4/SvJaeSor * C57BL/6N	MGI:6116294
cn38	Daam1^tm1.1Tpy/Daam1^tm1.1Tpy Nkx2-5^tm1(cre)Rjs/Nkx2-5^+ Wnt5a^tm1Amc/Wnt5a^tm1Amc	involves: 129S1/Sv * 129S7/SvEvBrd	MGI:6150926
cn39	Prox1^tm2Gco/Prox1^tm2Gco Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S1/Sv * 129S7/SvEvBrd	MGI:5907122
cn40	Zfpm2^tm1Sho/Zfpm2^tm2Sho Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S1/Sv * 129S7/SvEvBrd	MGI:3851399
cn41	Daam1^tm1.1Tpy/Daam1^tm1.1Tpy Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S1/Sv * 129S7/SvEvBrd	MGI:6150918
cn42	Daam1^tm1.1Tpy/Daam1^tm1.1Tpy Daam2^tm1Tpy/Daam2^tm1Tpy Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S1/Sv * 129S7/SvEvBrd	MGI:6150919
cn43	Daam1^tm1.1Tpy/Daam1^tm1.1Tpy Nkx2-5^tm1(cre)Rjs/Nkx2-5^+ Wnt5a^tm1Amc/Wnt5a^+	involves: 129S1/Sv * 129S7/SvEvBrd	MGI:6151066
cn44	Shh^tm1Chg/Shh^tm2Amc Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ	MGI:4843919
cn45	Hspb7^tm1.1Chen/Hspb7^tm1.1Chen Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ * C57BL/6	MGI:6159009
cn46	Hccs^tm1Tcc/Hccs^+ Nkx2-5^tm2(cre)Rph/Nkx2-5^+ Tg(CAG-EGFP)D4Nagy/0 Tg(Hmgcr-lacZ)H253Sest/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2	MGI:3826982
cn47	Gata4^tm1.1Sad/Gata4^tm1.1Sad Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:3783262
cn48	Nkx2-5^tm2(cre)Rph/Nkx2-5^+ Slmap^tm1.1Tuab/Slmap^tm1.1Tuab	involves: 129S1/Sv * C3H * C57BL/6	MGI:7704170
cn49	Bmp2^tm1Vrs/Bmp2^tm1Vrs Nkx2-5^tm2(cre)Rph/Nkx2-5^+	involves: 129S1/Sv * C57BL/6	MGI:3641420
cn50	Smyd2^tm1.1Fben/Smyd2^tm1.1Fben Nkx2-5^tm2(cre)Rph/Nkx2-5^+	involves: 129S1/Sv * C57BL/6	MGI:4441343
cn51	Srsf4^tm1c(EUCOMM)Wtsi/Srsf4^tm1c(EUCOMM)Wtsi Nkx2-5^tm2(cre)Rph/Nkx2-5^+	involves: 129S1/Sv * C57BL/6 * C57BL/6N	MGI:7610662
cn52	Bmp2^tm1Jfm/Bmp2^tm1Jfm Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S4/SvJaeSor	MGI:3620974
cn53	Bmp4^tm1Jfm/Bmp4^tm1.1Jfm Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S4/SvJaeSor * 129S7/SvEvBrd	MGI:3043044
cn54	Grk2^tm1Gwd/Grk2^tm1Gwd Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S4/SvJaeSor * 129S7/SvEvBrd * C57BL/6	MGI:3763210
cn55	Nkx2-5^tm1(cre)Rjs/Nkx2-5^+ Zic3^tm2.1Jwb/Y	involves: 129S4/SvJaeSor * 129S7/SvEvBrd * C57BL/6J	MGI:5470169
cn56	Gata4^tm1Sho/Gata4^tm1.1Wtp Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S6/SvEvTac * 129S7/SvEvBrd	MGI:3851408
cn57	Gata4^tm1Sho/Gata4^+ Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S6/SvEvTac * 129S7/SvEvBrd	MGI:3851410
cn58	Gata4^tm1.1Wtp/Gata4^tm1.1Wtp Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S7/SvEvBrd	MGI:3639276
cn59	Zic3^tm1.1Smwa/Y Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S7/SvEvBrd	MGI:5476840
cn60	Hand1^tm5Abfi/Hand1^+ Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S7/SvEvBrd	MGI:6766587
cn61	Ehmt1^tm2Yshk/Ehmt1^tm2Yshk Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S7/SvEvBrd	MGI:5543776
cn62	Fkbp1a^tm1.1Shou/Fkbp1a^tm1Zuk Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S7/SvEvBrd	MGI:5490242
cn63	Smo^tm2Amc/Smo^tm2.1Amc Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S7/SvEvBrd * 129X1/SvJ	MGI:4843927
cn64	Nkx2-5^tm1(cre)Rjs/Nkx2-5^+ Tbx1^tm1Bld/Tbx1^tm3Bld	involves: 129S7/SvEvBrd * C57BL/6	MGI:3046805
cn65	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
cn66	Foxc2^tm1.1Miu/Foxc2^tm1.1Miu Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S7/SvEvBrd * C57BL/6 * C57BL/6J * SJL	MGI:6879488
cn67	Adam17^tm1.1Wesh/Adam17^tm1.1Wesh Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S7/SvEvBrd * C57BL/6 * FVB/N	MGI:5571466
cn68	Yap1^tm1.1Eno/Yap1^tm1.1Eno Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S/SvEv	MGI:5446510
cn69	Pabir1^em1.1Yhua/Pabir1^em1.1Yhua Nkx2-5^em2(icre)Gpt/Nkx2-5^+	involves: C57BL/6 * C57BL/6JGpt	MGI:7547002
cx70	Nipbl^Gt(RRS564)Byg/Nipbl^+ Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129P2/OlaHsd * 129S7/SvEvBrd * CD-1	MGI:7492254
cx71	Nkx2-5^tm1Siz/Nkx2-5^+ Nkx2-6^tm1Siz/Nkx2-6^tm1Siz	involves: 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6J	MGI:3608505
cx72	Nkx2-5^tm4Rph/Nkx2-5^+ Tbx20^tm1.1Rph/Tbx20^+	involves: 129S1/Sv * C57BL/6	MGI:3579847
cx73	Nkx2-5^tm6Rph/Nkx2-5^+ Tg(DMPK/tetO-EGFP/DMPK)5-313Masm/0	involves: 129S1/Sv * FVB/N	MGI:3813456
cx74	Nkx2-5^tm6Rph/Nkx2-5^+ Tg(DMPK/tetO-EGFP/DMPK)5-313Masm/Tg(DMPK/tetO-EGFP/DMPK)5-313Masm	involves: 129S1/Sv * FVB/N	MGI:3813457
cx75	Nkx2-5^tm1(cre)Rjs/Nkx2-5^+ Nsd2^tm1Ykan/Nsd2^+	involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6	MGI:3851519
cx76	Cdc42^tm1.1Yizh/Cdc42^+ Nkx2-5^tm1Siz/Nkx2-5^+	involves: 129S4/SvJaeSor	MGI:5141005
cx77	Hand2^tm1Dsr/Hand2^+ Nkx2-5^tm1Wehi/Nkx2-5^+	involves: C57BL/6	MGI:3607708
cx78	Nkx2-5^tm3Rph/Nkx2-5^+ Tbx20^tm1.1Rph/Tbx20^+	involves: C57BL/6	MGI:3716381
cx79	Mrtfb^em1Dsr/Mrtfb^+ Myh7^em1Dsr/Myh7^+ Nkx2-5^em1Dsr/Nkx2-5^+	involves: C57BL/6J	MGI:6360225

Genotype
MGI:6314343

ht1

• Allelic Composition: Nkx2-5^tm1.1Krc/Nkx2-5⁺
• Genetic Background: 129S2.Cg(FVB)-Nkx2-5^tm1.1Krc

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

cardiovascular system

abnormal tricuspid valve morphology ( J:273096 )

• 11% of newborns exhibit incomplete delamination of tricuspid valve

abnormal tricuspid valve cusp morphology ( J:273096 )

• 6% of newborns exhibit apical displacement of septal leaflet of tricuspid valve

abnormal heart ventricle morphology ( J:273096 )

• 33% of newborns exhibit ventricular noncompaction

perimembraneous ventricular septal defect ( J:273096 )

• 33% of newborns exhibit perimembranous or muscular ventricular septal defects

muscular ventricular septal defect ( J:273096 )

• 33% of newborns exhibit perimembranous or muscular ventricular septal defects

mortality/aging

mortality/aging ( J:273096 )

N • perinatal death is not observed

Genotype
MGI:6294720

ht2

• Allelic Composition: Nkx2-5^tm1.1Hkas/Nkx2-5⁺
• Genetic Background: 129S2.Cg-Nkx2-5^tm1.1Hkas

mortality/aging

perinatal lethality, incomplete penetrance ( J:273096 )

• approximately 1/4 of mice die perinatally

cardiovascular system

abnormal heart morphology ( J:273096 )

• mice exhibit a variety of cardiac malformations that are described below

abnormal left posterior bundle morphology ( J:273097 )

• hearts exhibit an underdeveloped left bundle branch

• acetylcholine activity in left bundle branch is reduced in E18.5 hearts

abnormal atrioventricular node morphology ( J:273097 )

• mice exhibit reduced AV nodal size composed of smaller cardiomyocytes at 4 weeks of age but not at P1

double outlet right ventricle ( J:273096 )

abnormal tricuspid valve morphology ( J:273096 )

• about 50% of mice exhibit abnormal tricuspid valve, including Ebstein's malformation, in which the hinges of tricuspid valve leaflets are displayed towards the apex of the right ventricle, inappropriately delaminated or tethered tricuspid valves, and/or tricuspid valve atresia

Ebstein's malformation of tricuspid valve ( J:273096 )

tricuspid valve atresia ( J:273096 )

right atrial isomerism ( J:273096 )

• isomerism of the right atrial appendages

abnormal interatrial septum morphology ( J:273096 )

• P10 mice exhibit an atrial septal anomaly, with poorly developed flap valve and an increase in the size of the interatrial communication and foamen ovalis, with the maximum length of the septum primum being decreased

atrioventricular septal defect ( J:273096 )

• 3 mice exhibit atrioventricular septal defects

enlarged heart ( J:273096 )

abnormal heart ventricle morphology ( J:273096 )

• all newborns exhibit a prominent trabecular layer in ventricular walls indicative of ventricular noncompaction

perimembraneous ventricular septal defect ( J:273096 )

• 80% of mice exhibit perimembranous and/or muscular ventricular septum defects in single or multiple positions

abnormal interventricular septum muscular part morphology ( J:273096 )

• mice exhibit a failure of compaction of the muscular ventricular septum

muscular ventricular septal defect ( J:273096 )

• 80% of mice exhibit perimembranous and/or muscular ventricular septum defects in single or multiple positions

double chambered heart right ventricle ( J:273096 )

abnormal impulse conducting system conduction ( J:273097 )

• electrophysiology studies indicate decreased ventricular effective refractory period

abnormal atrioventricular node conduction ( J:273097 )

• electrophysiology studies indicate increased atrioventricular Wenckebach block cycle length, atrioventricular 2:1 conduction block cycle length, and atrioventricular effective refractory period indicating impaired AV node function

• however, sinus nodal function is not affected

atrioventricular block ( J:273097 )

• mice exhibit first degree atrioventricular (AV) block at 4 weeks, 7 months, and 17 months of age

• mice occasionally exhibit advanced AV block

prolonged PR interval ( J:273097 )

• PR interval is prolonged, indicating first degree AV block, is present at 4 weeks, 7 months, and 17 months of age, but not at P1

prolonged QRS complex duration ( J:273097 )

• mice at all ages exhibit a wide QRS, indicating prolonged ventricular conduction times

cardiomyopathy ( J:273096 )

muscle

abnormal left posterior bundle morphology ( J:273097 )

• hearts exhibit an underdeveloped left bundle branch

• acetylcholine activity in left bundle branch is reduced in E18.5 hearts

abnormal atrioventricular node morphology ( J:273097 )

• mice exhibit reduced AV nodal size composed of smaller cardiomyocytes at 4 weeks of age but not at P1

cardiomyopathy ( J:273096 )

homeostasis/metabolism

cyanosis ( J:273096 )

decreased acetylcholinesterase activity ( J:273097 )

• acetylcholinesterase activity in ventricular trabeculations and left bundle branch is reduced in E18.5 hearts

growth/size/body

right atrial isomerism ( J:273096 )

• isomerism of the right atrial appendages

enlarged heart ( J:273096 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congenital heart disease		DOID:1682		J:273097 , J:273096

Genotype
MGI:6294743

ht3

• Allelic Composition: Nkx2-5^tm1.1Hkas/Nkx2-5⁺
• Genetic Background: (129S2.Cg-Nkx2-5^tm1.1Hkas x C57BL/6)F1

cardiovascular system

cardiovascular system phenotype ( J:273096 )

N • Background Sensitivity: mice do not exhibit complex cardiac malformations such as atrioventricular septal defects as seen on the congenic 129S2/SvPas background

abnormal tricuspid valve cusp morphology ( J:273096 )

• Background Sensitivity: about 50% of mice exhibit subtle tricuspid valve leaflet abnormalities but abnormalities are much more subtle than on the congenic 129S2/SvPas background and no tricuspid atresia or Ebsteins malformation are seen

abnormal heart ventricle morphology ( J:273096 )

• 94% of mice exhibit ventricular noncompaction

perimembraneous ventricular septal defect ( J:273096 )

• Background Sensitivity: 50% of mice exhibit perimembranous and/or muscular ventricular septal defects in single or multiple positions, a lower percentage than on the congenic 129S2/SvPas background

muscular ventricular septal defect ( J:273096 )

• Background Sensitivity: 50% of mice exhibit perimembranous and/or muscular ventricular septal defects in single or multiple positions, a lower percentage than on the congenic 129S2/SvPas background

Genotype
MGI:5829832

ht4

• Allelic Composition: Nkx2-5^tm2.1Mwc/Nkx2-5⁺
• Genetic Background: B6J.Cg-Nkx2-5^tm2.1Mwc/Mwc

cardiovascular system

abnormal heart morphology ( J:239808 )

• right ventricular dysmorphism with a shift to the base, rounded apex, and misalignment relative to the left ventricle

atrioventricular node hypoplasia ( J:239808 )

• reduction in node size

abnormal heart apex morphology ( J:239808 )

dilated heart right atrium ( J:239808 )

patent cardiac foramen ovale ( J:239808 )

• in 71% of heterozgyous adults

decreased heart left ventricle weight ( J:239808 )

• distinct from heterozygotes with a proline substitution, these heterozygotes have decreased left ventrical mass

abnormal heart right ventricle morphology ( J:239808 )

dilated heart right ventricle ( J:239808 )

decreased cardiac stroke volume ( J:239808 )

• distinct from heterozygotes with a proline substitution, these heterozygotes have decreased left ventricular stroke volume

decreased heart ventricle muscle contractility ( J:239808 )

• heterozygotes have a signficant decrease in right ventricle ejection fraction as well as a decrease in left ventricular stroke volume and end diastolic volume

decreased heart left ventricle muscle contractility ( J:239808 )

decreased heart right ventricle muscle contractility ( J:239808 )

abnormal heart left ventricle pressure ( J:239808 )

• left ventricle shows decreased end diastolic volume, stroke volume, and heart mass

irregular heartbeat ( J:239808 )

abnormal heart electrocardiography waveform feature ( J:239808 )

• under homeostatic nonanesthetized conditions there is increased PQ and QRS and a small tendency for decreased ST intervals, and occasional arrhythmic episodes were observed with highly irregular PR intervals

abnormal PR interval ( J:239808 )

• wide variability in PR intervals in nonanesthetized electrocardiograms, with some showing increased PR

prolonged PQ interval ( J:239808 )

abnormal QRS complex ( J:239808 )

• wide variability in QRS intervals in nonanesthetized electrocardiograms, with some showing increased QRS

prolonged QRS complex duration ( J:239808 )

abnormal ST segment ( J:239808 )

• widened ST intervals

shortened ST segment ( J:239808 )

• small tendency for decreased ST interval

abnormal sinoatrial node conduction ( J:239808 )

sinoatrial block ( J:239808 )

muscle

atrioventricular node hypoplasia ( J:239808 )

• reduction in node size

decreased heart ventricle muscle contractility ( J:239808 )

• heterozygotes have a signficant decrease in right ventricle ejection fraction as well as a decrease in left ventricular stroke volume and end diastolic volume

decreased heart left ventricle muscle contractility ( J:239808 )

decreased heart right ventricle muscle contractility ( J:239808 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
atrial heart septal defect 7		DOID:0110112	OMIM:108900	J:239808
hypoplastic left heart syndrome		DOID:9955	OMIM:241550 OMIM:614435	J:239808
tetralogy of Fallot		DOID:6419	OMIM:187500	J:239808

Genotype
MGI:5882084

ht5

• Allelic Composition: Nkx2-5^tm3.1Mwc/Nkx2-5⁺
• Genetic Background: B6J.Cg-Nkx2-5^tm3.1Mwc/Mwc

cardiovascular system

dilated pulmonary artery ( J:239808 )

• E18.5 heart shows increased pulmonary artery diameter, but no abnormality in aortic diameter

abnormal heart morphology ( J:239808 )

• right ventricular dysmorphism with a shift to the base, rounded apex, and misalignment relative to the left ventricle

abnormal atrioventricular node morphology ( J:239808 )

• highly dysmorphic appearance of atrioventricular node region in heterozygotes

abnormal heart apex morphology ( J:239808 )

dilated heart right atrium ( J:239808 )

atrial septal defect ( J:239808 )

• 12% show atrial septal defects, which are not found in control or I183M mutant heterozygotes

patent cardiac foramen ovale ( J:239808 )

• in 88% of heterozgyous adults

abnormal heart right ventricle morphology ( J:239808 )

• at 15 weeks of age the right ventricle displays a shift to the base with a rounded apex relative to controls

dilated heart right ventricle ( J:239808 )

decreased heart right ventricle muscle contractility ( J:239808 )

• significant decrease in right ventricle ejection fraction

abnormal heart electrocardiography waveform feature ( J:239808 )

• under homeostatic nonanesthetized conditions there is increased PQ and QRS and a small tendency for decreased ST intervals, and 3 of 8 heterozygotes showed possible split QRS waves

prolonged PQ interval ( J:239808 )

prolonged QRS complex duration ( J:239808 )

shortened ST segment ( J:239808 )

• small tendency for decreased ST interval

abnormal sinoatrial node conduction ( J:239808 )

sinoatrial block ( J:239808 )

abnormal myocardial fiber physiology ( J:239808 )

• neonatal cardiomyocytes show a decrease in basal and maximal respiration compared with control cardiomyocytes

muscle

abnormal atrioventricular node morphology ( J:239808 )

• highly dysmorphic appearance of atrioventricular node region in heterozygotes

decreased heart right ventricle muscle contractility ( J:239808 )

• significant decrease in right ventricle ejection fraction

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
atrial heart septal defect 7		DOID:0110112	OMIM:108900	J:239808
hypoplastic left heart syndrome		DOID:9955	OMIM:241550 OMIM:614435	J:239808
tetralogy of Fallot		DOID:6419	OMIM:187500	J:239808

Genotype
MGI:3655274

ht6

• Allelic Composition: Nkx2-5^tm4Rph/Nkx2-5⁺
• Genetic Background: either: (involves: 129S1/Sv * 129T2/SvEms) or (involves: 129S1/Sv * C57BL/6J)

cardiovascular system

abnormal heart septum morphology ( J:81343 )

• Background Sensitivity: septal dysmorphogenesis is most severe on the 129/Sv background, with 17% of hearts showing severe septal malformations bordering on atrial septal defect

atrial septal aneurysm ( J:81343 )

• exhibit an increase in the frequency of atrial septal aneurysms, indicated by a ruffling of the valve over the foramen ovale

• Background Sensitivity: 11% of heterozygotes on the mixed 129S1/Sv and C57BL/6J background and 34% on the 129/Sv background exhibit atrial septal aneurysms

atrial septal defect ( J:81343 )

• only rarely exhibit an atrial septal defect

patent cardiac foramen ovale ( J:81343 )

• exhibit an increase in the frequency of patent foramen ovale, indicated by blood passing easily beneath the flap valve

• Background Sensitivity: 78% of adults (vs 26% of wild-type) on the mixed 129S1/Sv and C57BL/6J background while 94% of adults (vs. 74% of wild-type) on the 129/Sv background show patent foramen ovale

• all neonates on the C57BL/6J background have a patent foramen ovale and 25% of those have a foramen ovale that is up to 2-fold larger than its maximum size in wild-type

bicuspid aortic valve ( J:81343 )

• 2% have bicuspid aortic valves

Genotype
MGI:3655284

ht7

• Allelic Composition: Nkx2-5^tm4Rph/Nkx2-5⁺
• Genetic Background: either: (involves: 129S1/Sv * C57BL/6 * FVB/N) or (involves: 129S1/Sv * C57BL/6 * QS)

cardiovascular system

abnormal interatrial septum morphology ( J:81343 )

• exhibit an increase in patent foramen ovale and atrial septal aneurysms, indicating septum abnormalities

atrial septal aneurysm ( J:81343 )

• slight increase in atrial septal aneurysims (3% vs. 0% in wild-type)

patent cardiac foramen ovale ( J:81343 )

• Background Sensitivity: increase in frequency of patent foramen ovale, from 6% to 36% on the mixed C57BL/6 and Swiss background and from 2.65% to 62% on the mixed C57BL/6 and FVB/N background

Genotype
MGI:5426985

ht8

• Allelic Composition: Nkx2-5^tm1Wehi/Nkx2-5⁺
• Genetic Background: involves: 129P2/OlaHsd

hematopoietic system

spleen hypoplasia ( J:184521 )

immune system

spleen hypoplasia ( J:184521 )

Genotype
MGI:3655208

ht9

• Allelic Composition: Nkx2-5^tm1Wehi/Nkx2-5⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J * C57BL/10J

cardiovascular system

abnormal interatrial septum morphology ( J:81343 )

• delay or maldevelopment of the septum secundum and an increase in patent foramen ovale and atrial septal aneurysims

atrial septal aneurysm ( J:81343 )

• exhibit a 6-fold increase in atrial septal aneurysims (34.8% vs. 5.9% in wild-type); indicated by a ruffling of the valve over the foramen ovale

atrial septal defect ( J:81343 )

• only rarely exhibit an atrial septal defect

patent cardiac foramen ovale ( J:81343 )

• 3.5-fold increase in patent foramen ovale (66.1% vs. 18.9% of wild-type); indicated by blood passing easily beneath the flap valve

abnormal aortic valve commissure morphology ( J:81343 )

• in some cases, commissural fibrosis

bicuspid aortic valve ( J:81343 )

• exhibit a 7.8-fold increase in frequency of bicuspid aortic valves

thick aortic valve cusps ( J:81343 )

• mild leaflet thickening

aortic valve stenosis ( J:81343 )

• 3 of 35 display a 3-fold increase in blood flow velocity across the aortic valve suggesting aortic stenosis

prolonged PR interval ( J:81343 )

• females show a mild but significant prolongation of the PR interval

Genotype
MGI:3579848

ht10

• Allelic Composition: Nkx2-5^tm4Rph/Nkx2-5⁺
• Genetic Background: involves: 129S1/Sv

cardiovascular system

dilated heart left atrium ( J:98489 )

• left atrial dilation is seen

decreased heart left ventricle wall thickness ( J:98489 )

• left ventricular wall thickness was decreased by 12%

decreased heart left ventricle muscle contractility ( J:98489 )

• left ventricular systolic dimension was increased 27% and fractional shortening was decreased by 13%

muscle

decreased heart left ventricle muscle contractility ( J:98489 )

• left ventricular systolic dimension was increased 27% and fractional shortening was decreased by 13%

Genotype
MGI:6286233

ht11

• Allelic Composition: Nkx2-5^tm1.1Burg/Nkx2-5⁺
• Genetic Background: involves: 129S1/Sv * 129S2/SvPasCrl * 129X1/SvJ

mortality/aging

neonatal lethality, incomplete penetrance ( J:251389 )

• some newborn mice survive for only a few hours or until P1

postnatal lethality, incomplete penetrance ( J:251389 )

• premature death of up to 15% by 3 weeks of age

cardiovascular system

atrial septal defect ( J:251389 )

• 36% of P1 mice exhibit atrial septal defect

ostium secundum atrial septal defect ( J:251389 )

• 2 of 5 adult mice exhibit atrial septal defect in the septum secundum

abnormal heart ventricle morphology ( J:251389 )

• some P1 hearts exhibit abnormal ventricular wall

ventricular septal defect ( J:251389 )

• 3 of 5 adult mice exhibit ventricular septal defect

atrioventricular block ( J:251389 )

• more than 50% of 16-20 week old mice exhibit 1st degree AV block

• 2 of 12 mice exhibit 2nd degree AV block

• however, echocardiography of 16-20 week old mice shows no contractile dysfunction or dilation of hearts

prolonged PR interval ( J:251389 )

• more than 50% of 16-20 week old mice exhibit prolonged PR interval, an indication of 1st degree AV block

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congenital heart disease		DOID:1682		J:251389

Genotype
MGI:3041124

ht12

• Allelic Composition: Nkx2-5^tm2Siz/Nkx2-5⁺
• Genetic Background: involves: 129S4/SvJaeSor

cardiovascular system

abnormal impulse conducting system morphology ( J:89216 )

• form a smaller central conduction system, with smaller atrioventricular node and His bundle

• the number of cells in the conduction system is reduced by approximately half

abnormal Purkinje fiber morphology ( J:89216 )

• hypocellularity of the peripheral Purkinje network

abnormal atrioventricular node morphology ( J:89216 )

• smaller atrioventricular node

abnormal heart development ( J:89216 )

heart block ( J:89216 )

• defects in in the atrioventricular node, His bundle, and intraventricular conduction

• exhibit similar conduction and electrophysiologic abnormalities as heterozygous Nkx2-5^tm1Siz mice

muscle

abnormal impulse conducting system morphology ( J:89216 )

• form a smaller central conduction system, with smaller atrioventricular node and His bundle

• the number of cells in the conduction system is reduced by approximately half

abnormal Purkinje fiber morphology ( J:89216 )

• hypocellularity of the peripheral Purkinje network

abnormal atrioventricular node morphology ( J:89216 )

• smaller atrioventricular node

Genotype
MGI:3623792

ht13

• Allelic Composition: Nkx2-5^tm1Siz/Nkx2-5⁺
• Genetic Background: involves: 129S4/SvJaeSor

cardiovascular system

abnormal Purkinje fiber morphology ( J:89216 )

• ventricles have approximately half as many Purkinje cells as wild-type

decreased heart ventricle muscle contractility ( J:174208 )

• at 8 and 12 weeks, mice exhibit decreased fractional shortening and ejection fraction compared with wild-type mice

abnormal impulse conducting system conduction ( J:89216 )

• longer 1:1 and 2:1 cycle lengths and atrioventricular node effective refractory periods than wild-type as determined by rapid atrial pacing

• His signal amplitude on the IEGM is markedly diminished in heterozygotes as young as 3 weeks

atrioventricular block ( J:89216 )

• diminished AV node function

• heterozygotes as old as 2 years, do not progress beyond first-degree AV block

prolonged PR interval ( J:89216 )

• prolonged PR interval at 7 weeks of age or older resulting from prolongation of the AH interval

prolonged QRS complex duration ( J:89216 , J:174208 )

• prolonged QRS interval at all ages (J:89216)

muscle

abnormal Purkinje fiber morphology ( J:89216 )

• ventricles have approximately half as many Purkinje cells as wild-type

decreased heart ventricle muscle contractility ( J:174208 )

• at 8 and 12 weeks, mice exhibit decreased fractional shortening and ejection fraction compared with wild-type mice

Genotype
MGI:6368032

cn14

• 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)

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

cn15

• 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:7341797

cn16

• Allelic Composition: Dicer1^tm1Bdh/Dicer1^tm1Bdh; Nkx2-5^tm2(cre)Rph/Nkx2-5⁺
• Genetic Background: involves: 129 * 129S1/Sv

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:156467 )

• embryos are present at Mendelian ratios up to E13.5, but fail to survive past E13.7; only 10% are recovered at E13.7-E14.0 and those found alive are close to expiration

cardiovascular system

thin ventricle myocardium compact layer ( J:156467 )

• a thin, improperly compacted ventricular myocardium is observed at E13.0

• however, no significant increase in cell death is noted in the abnormal myocardium

abnormal cardiac outflow tract development ( J:156467 )

• mRNA levels of Pitx2 (critical in the establishment of OFT positioning relative to the ventricles) are upregulated in the OFT and adjacent ventricular wall starting from E10.25 and as late as E13.0

• mRNA expression of Sema3c is upregulated in the OFT and adjacent ventricular wall starting at E12.5

• mesenchymal apoptosis is significantly reduced in the OFT at E13.0 and E13.5, but not at E12.5 or earlier; a ~5-fold decrease in mesenchymal cell death is noted in the OFT at E12.75-E13.0

• however, no change in cell proliferation is detected at E12.0, E12.5 or E13.0

double outlet right ventricle ( J:156467 )

• by E13.0-E13.5, fifteen of 19 (79%) of hearts exhibit DORV with a concurrent ventricular septal defect (VSD)

ventricular septal defect ( J:156467 )

• by E13.0-E13.5, fifteen of 19 (79%) of hearts exhibit DORV with a concurrent VSD

muscle

thin ventricle myocardium compact layer ( J:156467 )

• a thin, improperly compacted ventricular myocardium is observed at E13.0

• however, no significant increase in cell death is noted in the abnormal myocardium

Genotype
MGI:7550409

cn17

• Allelic Composition: Sox7^tm1.1Nat/Sox7^tm1.1Nat; Nkx2-5^tm2(cre)Rph/Nkx2-5⁺
• Genetic Background: involves: 129 * 129S1/Sv * C57BL/6 * SJL

cardiovascular system

abnormal cardiac epithelial to mesenchymal transition ( J:306193 )

atrioventricular cushion hypoplasia ( J:306193 )

• at E9.5, atrioventricular (AV) cushions exhibit significantly lower numbers of mesenchymal cells than control AV cushions, suggesting disruption of endothelial to mesenchymal transition (EndMT)

Genotype
MGI:3818073

cn18

• 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:4430398

cn19

• 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

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:5575766

cn20

• 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

cn21

• 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

cn22

• 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:5426979

cn23

• Allelic Composition: Nkx2-5^tm2(cre)Rph/Nkx2-5⁺; Pbx1^tm1.1Koss/Pbx1^tm1.1Koss
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv

hematopoietic system

abnormal spleen morphology ( J:184521 )

• hypoplastic and fragmented

spleen hypoplasia ( J:184521 )

immune system

abnormal spleen morphology ( J:184521 )

• hypoplastic and fragmented

spleen hypoplasia ( J:184521 )

Genotype
MGI:5426980

cn24

• Allelic Composition: Pbx1^tm1Koss/Pbx1^tm1Koss; Nkx2-5^tm2(cre)Rph/Nkx2-5⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv

hematopoietic system

abnormal spleen morphology ( J:184521 )

• hypoplastic and fragmented

abnormal spleen mesenchyme morphology ( J:184521 )

• significant decrease of mitotic mesenchymal cells in the anlagen

spleen hypoplasia ( J:184521 )

immune system

abnormal spleen morphology ( J:184521 )

• hypoplastic and fragmented

abnormal spleen mesenchyme morphology ( J:184521 )

• significant decrease of mitotic mesenchymal cells in the anlagen

spleen hypoplasia ( J:184521 )

Genotype
MGI:5426986

cn25

• Allelic Composition: Cdkn2b^tm1Bbd/Cdkn2b^tm1Bbd; Pbx1^tm1Koss/Pbx1^tm1Koss; Nkx2-5^tm2(cre)Rph/Nkx2-5⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv

hematopoietic system

abnormal spleen morphology ( J:184521 )

• partial rescue of spleen expansion compared to mutant mice wild-type for Cdkn2b and spleens form a single compact anlage

abnormal spleen mesenchyme morphology ( J:184521 )

• significant rescue of mesenchymal proliferation compared to mutant mice wild-type for Cdkn2b

immune system

abnormal spleen morphology ( J:184521 )

• partial rescue of spleen expansion compared to mutant mice wild-type for Cdkn2b and spleens form a single compact anlage

abnormal spleen mesenchyme morphology ( J:184521 )

• significant rescue of mesenchymal proliferation compared to mutant mice wild-type for Cdkn2b

Genotype
MGI:3818077

cn26

• 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:3818072

cn27

• 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:5707467

cn28

• 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:5811817

cn29

• 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

cn30

• 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

cn31

• 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:5426982

cn32

• Allelic Composition: Pbx1^tm1Koss/Pbx1^tm1Koss; Pbx2^tm1Mlc/Pbx2⁺; Nkx2-5^tm2(cre)Rph/Nkx2-5⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S/Sv * 129S1/Sv

hematopoietic system

abnormal spleen morphology ( J:184521 )

• hypoplastic and fragmented

• more severe than in mutant mice wild-type for Pbx2

spleen hypoplasia ( J:184521 )

immune system

abnormal spleen morphology ( J:184521 )

• hypoplastic and fragmented

• more severe than in mutant mice wild-type for Pbx2

spleen hypoplasia ( J:184521 )

Genotype
MGI:3826965

cn33

• Allelic Composition: Hccs^tm1Tcc/Hccs^tm1Tcc; Nkx2-5^tm2(cre)Rph/Nkx2-5⁺
• Genetic Background: involves: 129S1/Sv

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:143285 )

♀ • most die between E10.5 and E12.5 with few surviving to die by E14.5

Genotype
MGI:3826966

cn34

• Allelic Composition: Hccs^tm1Tcc/Y; Nkx2-5^tm2(cre)Rph/Nkx2-5⁺
• Genetic Background: involves: 129S1/Sv

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:143285 )

♂ • most die between E10.5 and E12.5 with few surviving to die by E14.5

cardiovascular system

decreased cardiac muscle glycogen level ( J:143285 )

♂ • at E13.5, glycogen storage in embryonic hearts is decreased compared to in wild-type mice

abnormal fetal cardiomyocyte morphology ( J:143285 )

♂ • at E13.5, the degree of cardiomyocyte differentiation towards the ventricular lumen is lower than in wild-type mice

♂ • at E13.5, cardiomyocytes have less mature sarcomeres with shorter, randomly arranged muscle fibrils unlike in wild-type mice

♂ • however, mice exhibit normal cardiac morphology at E10.5 and E12.5

♂ • at E13.5, cardiomyocytes accumulate a fine granular material unlike in wild-type cells

abnormal fetal cardiomyocyte mitochondrial morphology ( J:143285 )

♂ • at E13.5, a subset of cardiomyocytes contain irregular mitochondria

decreased fetal cardiomyocyte proliferation ( J:143285 )

♂ • at E11.5, proliferation of cardiomyocytes is decreased 45% compared to in wild-type mice

cellular

abnormal fetal cardiomyocyte mitochondrial morphology ( J:143285 )

♂ • at E13.5, a subset of cardiomyocytes contain irregular mitochondria

decreased fetal cardiomyocyte proliferation ( J:143285 )

♂ • at E11.5, proliferation of cardiomyocytes is decreased 45% compared to in wild-type mice

abnormal respiratory electron transport chain ( J:143285 )

♂ • at E12.5 and E14.5, respiratory chain complex III activity in cardiomyocytes is 10% of normal

homeostasis/metabolism

decreased cardiac muscle glycogen level ( J:143285 )

♂ • at E13.5, glycogen storage in embryonic hearts is decreased compared to in wild-type mice

muscle

decreased cardiac muscle glycogen level ( J:143285 )

♂ • at E13.5, glycogen storage in embryonic hearts is decreased compared to in wild-type mice

abnormal fetal cardiomyocyte mitochondrial morphology ( J:143285 )

♂ • at E13.5, a subset of cardiomyocytes contain irregular mitochondria

decreased fetal cardiomyocyte proliferation ( J:143285 )

♂ • at E11.5, proliferation of cardiomyocytes is decreased 45% compared to in wild-type mice

Genotype
MGI:3826967

cn35

• Allelic Composition: Hccs^tm1Tcc/Hccs⁺; Nkx2-5^tm2(cre)Rph/Nkx2-5⁺
• Genetic Background: involves: 129S1/Sv

mortality/aging

premature death ( J:143285 )

♀ • 13% of mice die between 9 and 15 months of age with varying degrees of dilated cardiomyopathy

♀ • however, mice exhibit no embryonic lethality

cardiovascular system

abnormal myocardium layer morphology ( J:143285 )

♀ • at 8 weeks, pale and granulated cells resembling degenerating cardiomyocytes are found in the ventricular myocardium unlike in wild-type mice

♀ • at 1 year, severely affected mice exhibit hypertrophic cardiocyocytes

abnormal fetal cardiomyocyte mitochondrial morphology ( J:143285 )

♀ • at E13.5, a subset of cardiomyocytes contain irregular mitochondria

♀ • however, no other cardiac abnormalities are observed at E13.5

dilated heart atrium ( J:143285 )

♀ • in severely affected mice at 1 year

enlarged heart ( J:143285 )

♀ • in severely affected mice at 1 year

dilated heart left ventricle ( J:143285 )

♀ • in severely affected mice at 1 year

thick ventricular wall ( J:143285 )

♀ • in mice with hypertrophic cardiomyocytes at 1 year

dilated heart right ventricle ( J:143285 )

♀ • in severely affected mice at 1 year

cardiac interstitial fibrosis ( J:143285 )

♀ • at 1 year, mice with dilated cardiomyopathy exhibit increased interstitial fibrosis compared to mice that develop a hypertrophic cardiomyocyte-like phenotype

dilated cardiomyopathy ( J:143285 )

♀ • in severely affected mice at 1 year

atrioventricular block ( J:143285 )

♀ • at 1 year, 40% of mice exhibit pathologies of the cardiac conduction system including first degree atrioventricular (AV) block or intermittent second degree AV block type II

sinoatrial block ( J:143285 )

♀ • at 1 year, 40% of mice exhibit pathologies of the cardiac conduction system including sinus bradycardia

bundle branch block ( J:143285 )

♀ • at 1 year, 40% of mice exhibit pathologies of the cardiac conduction system including transient bundle branch block

abnormal myocardial fiber physiology ( J:143285 )

♀ • respiratory chain complex III activity in cardiomyocytes is reduced 43% at E12.5 and 56% at E14.5 compared to in wild-type cells

♀ • however, cardiomyocytes is reduced at 8 weeks is normal

cellular

abnormal fetal cardiomyocyte mitochondrial morphology ( J:143285 )

♀ • at E13.5, a subset of cardiomyocytes contain irregular mitochondria

♀ • however, no other cardiac abnormalities are observed at E13.5

cardiac interstitial fibrosis ( J:143285 )

♀ • at 1 year, mice with dilated cardiomyopathy exhibit increased interstitial fibrosis compared to mice that develop a hypertrophic cardiomyocyte-like phenotype

abnormal respiratory electron transport chain ( J:143285 )

♀ • respiratory chain complex III activity in cardiomyocytes is reduced 43% at E12.5 and 56% at E14.5 compared to in wild-type cells

♀ • however, cardiomyocytes is reduced at 8 weeks is normal

homeostasis/metabolism

abnormal atrial thrombosis ( J:143285 )

♀ • in severely affected mice at 1 year

muscle

abnormal myocardium layer morphology ( J:143285 )

♀ • at 8 weeks, pale and granulated cells resembling degenerating cardiomyocytes are found in the ventricular myocardium unlike in wild-type mice

♀ • at 1 year, severely affected mice exhibit hypertrophic cardiocyocytes

abnormal fetal cardiomyocyte mitochondrial morphology ( J:143285 )

♀ • at E13.5, a subset of cardiomyocytes contain irregular mitochondria

♀ • however, no other cardiac abnormalities are observed at E13.5

dilated cardiomyopathy ( J:143285 )

♀ • in severely affected mice at 1 year

growth/size/body

enlarged heart ( J:143285 )

♀ • in severely affected mice at 1 year

Genotype
MGI:6150944

cn36

• 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:6116294

cn37

• Allelic Composition: Gas2l3^{tm1c(EUCOMM)Hmgu}/Gas2l3^{tm1c(EUCOMM)Hmgu}; Nkx2-5^tm2(cre)Rph/Nkx2-5⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJaeSor * C57BL/6N

cardiovascular system

increased heart weight ( J:244087 )

• increase in heart to body weight ratio

cardiac interstitial fibrosis ( J:244087 )

dilated heart ( J:244087 )

dilated cardiomyopathy ( J:244087 )

muscle

dilated cardiomyopathy ( J:244087 )

growth/size/body

increased heart weight ( J:244087 )

• increase in heart to body weight ratio

cellular

cardiac interstitial fibrosis ( J:244087 )

Genotype
MGI:6150926

cn38

• 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:5907122

cn39

• 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 heart ventricle 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 heart ventricle 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:3851399

cn40

• 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:6150918

cn41

• 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 )

• 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

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

Genotype
MGI:6150919

cn42

• 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:6151066

cn43

• 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:4843919

cn44

• 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

cn45

• 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:3826982

cn46

• Allelic Composition: Hccs^tm1Tcc/Hccs⁺; Nkx2-5^tm2(cre)Rph/Nkx2-5⁺; Tg(CAG-EGFP)D4Nagy/0; Tg(Hmgcr-lacZ)H253Sest/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2

cardiovascular system

abnormal fetal cardiomyocyte morphology ( J:143285 )

♀ • at E12.5, the relative volume of abnormal heart tissue begins to decline to 42% in ventricles and 47% in atria and is further reduced at E16.5 to 18% in ventricles and 19% in the atria then 10% in ventricles and 17% in the atria prior to birth

♀ • at E12.5 and E13.5, cardiomyocytes appear small and round compared to wild-type cells

♀ • however, the absolute volume of heart tissue before birth is unchanged

decreased fetal cardiomyocyte size ( J:143285 )

♀ • cardiomyocytes appear smaller at E12.5 and E13.5

abnormal fetal cardiomyocyte proliferation ( J:143285 )

♀ • while the number of affected cardiomyocytes decreases proliferation of normal cardiomyocytes increases in a compensatory manner

muscle

abnormal fetal cardiomyocyte proliferation ( J:143285 )

♀ • while the number of affected cardiomyocytes decreases proliferation of normal cardiomyocytes increases in a compensatory manner

cellular

abnormal fetal cardiomyocyte proliferation ( J:143285 )

♀ • while the number of affected cardiomyocytes decreases proliferation of normal cardiomyocytes increases in a compensatory manner

Genotype
MGI:3783262

cn47

• 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

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:7704170

cn48

• Allelic Composition: Nkx2-5^tm2(cre)Rph/Nkx2-5⁺; Slmap^tm1.1Tuab/Slmap^tm1.1Tuab
• Genetic Background: involves: 129S1/Sv * C3H * C57BL/6

cardiovascular system

cardiovascular system phenotype ( J:346063 )

N • no abnormalities are detected in cardiomyocyte proliferation during cardiogenesis

N • no abnormalities detected in adult cardiac function or morphology

abnormal atrioventricular cushion morphology ( J:346063 )

• delay in septation indicated by absence of cushion of the atrioventricular cushions at E12.5

• however, by E16.5 septation is complete

decreased fetal cardiomyocyte size ( J:346063 )

• at E12.5 in the left ventricle

decreased heart atrium wall thickness ( J:346063 )

small heart ( J:346063 )

• significantly smaller at E9.5, E12.5, and E16.5

• however, by P0 and P7 heart size is similar to wild-type controls

thin ventricular wall ( J:346063 )

decreased heart left ventricle wall thickness ( J:346063 )

• significantly thinner at E9.5, E12.5, and E16.5

• however, by P7 wall thickness is similar to wild-type controls

Genotype
MGI:3641420

cn49

• Allelic Composition: Bmp2^tm1Vrs/Bmp2^tm1Vrs; Nkx2-5^tm2(cre)Rph/Nkx2-5⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:110615 )

• conditional Bmp2 deletion results in death by E11.5; embryos are alive at E10.5

embryo

decreased embryo size ( J:110615 )

• conditional Bmp2-null embryos are smaller than wild-type controls at E10.5

growth/size/body

decreased embryo size ( J:110615 )

• conditional Bmp2-null embryos are smaller than wild-type controls at E10.5

cardiovascular system

abnormal heart development ( J:110615 )

• at E10.5, embryos have an abnormally patterned heart with an uncharacteristic, straight morphology to the region between the atria and ventricles

absent atrioventricular cushions ( J:110615 )

• endocardial cushions and EC mesenchyme are missing at E10.5, as well as the AV constriction

pericardial effusion ( J:110615 )

• some embryos show pericardial effusion

homeostasis/metabolism

pericardial effusion ( J:110615 )

• some embryos show pericardial effusion

cardiac edema ( J:110615 )

• some embryos show cardiac edema

Genotype
MGI:4441343

cn50

• Allelic Composition: Smyd2^tm1.1Fben/Smyd2^tm1.1Fben; Nkx2-5^tm2(cre)Rph/Nkx2-5⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6

cardiovascular system

cardiovascular system phenotype ( J:158898 )

N • no defects are detected in cardiac morphology or function

Genotype
MGI:7610662

cn51

• Allelic Composition: Srsf4^{tm1c(EUCOMM)Wtsi}/Srsf4^{tm1c(EUCOMM)Wtsi}; Nkx2-5^tm2(cre)Rph/Nkx2-5⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6 * C57BL/6N
• Cell Lines: EPD0039_1_C07

cardiovascular system

cardiovascular system phenotype ( J:344969 )

N • mice have normal systolic and diastolic blood pressure at 2, 4, and 10 months of age

increased myocardial fiber size ( J:344969 )

• cardiomyocyte cross-sectional area (CSA) is significantly increased at 2 and 4 months of age

increased fetal cardiomyocyte size ( J:344969 )

• after treatment with dexamethasone (DEX), neonatal cardiomyocytes show significantly higher mRNA levels of hypertrophy markers (Nppa, Nppb) and direct glucocorticoid receptor targets (Fkbp5, Tsc22d3), and have a significantly larger surface area than both DEX-treated control cells and untreated cells, indicating increased glucocorticoid-induced cardiomyocyte hypertrophy

• GAS5 overexpression in neonatal cardiomyocytes significantly decreases DEX-induced expression of Nppa (and to a lesser extent of Tsc22d3) and reduces DEX-induced cardiomyocyte hypertrophy by decreasing their surface area

enlarged heart ( J:344969 )

• whole hearts are overtly enlarged at 10 months of age

heart left ventricle hypertrophy ( J:344969 )

• mice develop LV hypertrophy with significantly increased LV wall thickness, LV mass, cardiomyocyte cross-sectional area, and mRNA levels of heart disease markers Nppb (natriuretic peptide type B, aka Bnp) and Myh7 (myosin, heavy polypeptide 7, cardiac muscle, beta)

• after 2 wks of treatment with DEX, mice show significantly higher mRNA levels of hypertrophy markers (Nppa) and glucocorticoid receptor targets (Fkbp5, Tsc22d3) than both DEX-treated control mice and untreated mice

• GAS5 overexpression via injection of AAV9-GAS5 significantly decreases LV wall thickness and partially reduces expression of Fkbp5 and Tsc22d3 at day 7 post-injection

• however, untreated mice show normal mRNA levels of fibrosis markers and no increase in cardiac fibrosis from 2 to 14 months of age; mRNA and protein expression of Nr3c1 (aka glucocorticoid receptor, GR) is similar to that in control hearts from 2 to 8 months

increased heart weight ( J:344969 )

• mice show a significant increase in normalized cardiac mass and heart weight to body weight (HW/BW) ratio at 10 and 14 months of age; however, BW is normal from 6 to 14 months of age

• after 2 wks of treatment with DEX, mice show a significantly higher HW/BW ratio than both DEX-treated control mice and untreated mice

increased heart left ventricle weight ( J:344969 )

• mice show significantly increased LV mass at 10 and 14 months of age

increased heart left ventricle wall thickness ( J:344969 )

• mice show significantly increased left ventricular (LV) wall thickness at 10 and 14 months of age; LV wall is also thicker than that in control Nkx2-5 heterozygotes

• 6-wk-old mice treated with DEX for 14 days show a significantly thicker LV wall than both DEX-treated control mice and untreated mice

abnormal cardiovascular system physiology ( J:344969 )

• hearts show significantly decreased mRNA levels of Gas5 (growth arrest specific 5), an inhibitor of the glucocorticoid receptor, from P1 to 6 months of age

abnormal fetal cardiomyocyte physiology ( J:344969 )

• after treatment with a nonsense-mediated decay (NMD) inhibitor, neonatal cardiomyocytes show an even greater increase in Gas5 mRNA levels than similarly treated control cells, suggesting that SRSF4 binds GAS5 and protects it from degradation by NMD

abnormal heart echocardiography feature ( J:344969 )

• mice show progressive diastolic dysfunction, as indicated by a significant and age-dependent reduction in the E/A wave ratio of mitral flow and an elevated isovolumetric relaxation time (IVRT) at 14 months of age

• however, LV ejection fraction (LVEF) and LV diastolic volume (LVVOLd) are normal from 6 to 14 months

abnormal mitral valve flow ( J:344969 )

• mice exhibit a significant reduction in the early and late diastolic peak wave ratio (E/A wave ratio of mitral flow) at 14 months of age

increased heart rate ( J:344969 )

• at 6 months of age, mice exhibit a significantly higher heart rate than controls both under basal and isoproterenol-induced stress conditions

abnormal heart electrocardiography waveform feature ( J:344969 )

• under isoproterenol-induced stress conditions, mice exhibit a negative J wave at 6 months of age

• J wave amplitude is also decreased under basal conditions but the difference is not statistically significant

increased QRS amplitude ( J:344969 )

• under basal conditions, mice exhibit a wider QRS complex amplitude than controls at 6 months of age

• QRS amplitude is also wider under isoproterenol-induced stress conditions but the difference is not statistically significant

prolonged QT interval ( J:344969 )

• under isoproterenol-induced stress conditions, mice exhibit a significantly prolonged cQT (= QT interval corrected for heart rate) at 6 months of age

• cQT is also longer under basal conditions but the difference is not statistically significant

shortened ST segment ( J:344969 )

• under isoproterenol-induced stress conditions, mice exhibit a significantly depressed ST-segment at 6 months of age

increased response of heart to induced stress ( J:344969 )

• in response to isoproterenol-induced stress, 6-mo-old mice show more severe electrocardiographic features of cardiac hypertrophy and abnormal repolarization, with a further increase in the cQT interval, marked ST-segment depression, and a negative J wave

growth/size/body

enlarged heart ( J:344969 )

• whole hearts are overtly enlarged at 10 months of age

heart left ventricle hypertrophy ( J:344969 )

• mice develop LV hypertrophy with significantly increased LV wall thickness, LV mass, cardiomyocyte cross-sectional area, and mRNA levels of heart disease markers Nppb (natriuretic peptide type B, aka Bnp) and Myh7 (myosin, heavy polypeptide 7, cardiac muscle, beta)

• after 2 wks of treatment with DEX, mice show significantly higher mRNA levels of hypertrophy markers (Nppa) and glucocorticoid receptor targets (Fkbp5, Tsc22d3) than both DEX-treated control mice and untreated mice

• GAS5 overexpression via injection of AAV9-GAS5 significantly decreases LV wall thickness and partially reduces expression of Fkbp5 and Tsc22d3 at day 7 post-injection

• however, untreated mice show normal mRNA levels of fibrosis markers and no increase in cardiac fibrosis from 2 to 14 months of age; mRNA and protein expression of Nr3c1 (aka glucocorticoid receptor, GR) is similar to that in control hearts from 2 to 8 months

increased heart weight ( J:344969 )

• mice show a significant increase in normalized cardiac mass and heart weight to body weight (HW/BW) ratio at 10 and 14 months of age; however, BW is normal from 6 to 14 months of age

• after 2 wks of treatment with DEX, mice show a significantly higher HW/BW ratio than both DEX-treated control mice and untreated mice

muscle

increased myocardial fiber size ( J:344969 )

• cardiomyocyte cross-sectional area (CSA) is significantly increased at 2 and 4 months of age

heart left ventricle hypertrophy ( J:344969 )

• mice develop LV hypertrophy with significantly increased LV wall thickness, LV mass, cardiomyocyte cross-sectional area, and mRNA levels of heart disease markers Nppb (natriuretic peptide type B, aka Bnp) and Myh7 (myosin, heavy polypeptide 7, cardiac muscle, beta)

• after 2 wks of treatment with DEX, mice show significantly higher mRNA levels of hypertrophy markers (Nppa) and glucocorticoid receptor targets (Fkbp5, Tsc22d3) than both DEX-treated control mice and untreated mice

• GAS5 overexpression via injection of AAV9-GAS5 significantly decreases LV wall thickness and partially reduces expression of Fkbp5 and Tsc22d3 at day 7 post-injection

• however, untreated mice show normal mRNA levels of fibrosis markers and no increase in cardiac fibrosis from 2 to 14 months of age; mRNA and protein expression of Nr3c1 (aka glucocorticoid receptor, GR) is similar to that in control hearts from 2 to 8 months

homeostasis/metabolism

increased response of heart to induced stress ( J:344969 )

• in response to isoproterenol-induced stress, 6-mo-old mice show more severe electrocardiographic features of cardiac hypertrophy and abnormal repolarization, with a further increase in the cQT interval, marked ST-segment depression, and a negative J wave

Genotype
MGI:3620974

cn52

• 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

cn53

• 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

cn54

• 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

cn55

• 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

cn56

• 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

cn57

• 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:3639276

cn58

• 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

decreased 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

decreased 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

decreased fetal cardiomyocyte proliferation ( J:99203 )

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

Genotype
MGI:5476840

cn59

• 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

cn60

• 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

cn61

• 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:5490242

cn62

• 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:4843927

cn63

• 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:3046805

cn64

• 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

cn65

• 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 myocardial fiber apoptosis ( J:233994 )

• at P20

cellular

increased fetal cardiomyocyte proliferation ( J:233994 )

• at E18.5

increased myocardial fiber 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 myocardial fiber 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

cn66

• 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

cn67

• 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:5446510

cn68

• 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:7547002

cn69

• Allelic Composition: Pabir1^em1.1Yhua/Pabir1^em1.1Yhua; Nkx2-5^em2(icre)Gpt/Nkx2-5⁺
• Genetic Background: involves: C57BL/6 * C57BL/6JGpt

cardiovascular system

decreased heart weight ( J:337007 )

• the heart weight to body weight is decreased indicating a decrease in heart weight

growth/size/body

decreased body weight ( J:337007 )

Genotype
MGI:7492254

cx70

• 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:3608505

cx71

• Allelic Composition: Nkx2-5^tm1Siz/Nkx2-5⁺; Nkx2-6^tm1Siz/Nkx2-6^tm1Siz
• Genetic Background: involves: 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6J

normal phenotype

no abnormal phenotype detected ( J:69976 )

• mice heterozygous for Nkx2-5^tm1Siz and homozygous for Nkx2-6^tm1Siz are viable and fertile and display no detectable abnormalities either in pharynx or in heart

Genotype
MGI:3579847

cx72

• Allelic Composition: Nkx2-5^tm4Rph/Nkx2-5⁺; Tbx20^tm1.1Rph/Tbx20⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6

mortality/aging

preweaning lethality, incomplete penetrance ( J:98489 )

• only 10% of mice at weaning were double heterozygotes suggesting partial embryonic or perinatal lethality

cardiovascular system

myocardial fiber disarray ( J:98489 )

• some adult mice with atrial septal defects also display myocyte disarray

dilated heart left atrium ( J:98489 )

• left atrial dilation is seen

atrial septal defect ( J:98489 )

• 16% of double heterozygotes had atrial septal defects

decreased heart left ventricle wall thickness ( J:98489 )

• left ventricular wall thickness was decreased by 40%

dilated heart left ventricle ( J:98489 )

• the left ventricle diastolic dimension is mildly but significantly increased

cardiac fibrosis ( J:98489 )

• some adult mice with atrial septal defects also display patches of fibrosis in the right ventricular myocardium

dilated cardiomyopathy ( J:98489 )

• signs of dilated cardiomyopathy are seen but no compensatory myocardial hypertrophy or change in heart weight are detected

decreased heart left ventricle muscle contractility ( J:98489 )

• left ventricular systolic dimension was increased 47% and fractional shortening was decreased by 24%

muscle

myocardial fiber disarray ( J:98489 )

• some adult mice with atrial septal defects also display myocyte disarray

dilated cardiomyopathy ( J:98489 )

• signs of dilated cardiomyopathy are seen but no compensatory myocardial hypertrophy or change in heart weight are detected

decreased heart left ventricle muscle contractility ( J:98489 )

• left ventricular systolic dimension was increased 47% and fractional shortening was decreased by 24%

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
atrial heart septal defect 1		DOID:0110106	OMIM:108800	J:98489

Genotype
MGI:3813456

cx73

• Allelic Composition: Nkx2-5^tm6Rph/Nkx2-5⁺; Tg(DMPK/tetO-EGFP/DMPK)5-313Masm/0
• Genetic Background: involves: 129S1/Sv * FVB/N

muscle

impaired muscle relaxation ( J:131302 )

• by 3 weeks of treatment with doxycycline, mice exhibit myotonia

cardiovascular system

prolonged PR interval ( J:131302 )

• at 2 weeks post treatment with doxycycline, mice exhibit a less dramatic increase in PR intervals than in Tg(DMPK/tetO-GFP/DMPK)5-313Masm mice

Genotype
MGI:3813457

cx74

• Allelic Composition: Nkx2-5^tm6Rph/Nkx2-5⁺; Tg(DMPK/tetO-EGFP/DMPK)5-313Masm/Tg(DMPK/tetO-EGFP/DMPK)5-313Masm
• Genetic Background: involves: 129S1/Sv * FVB/N

muscle

impaired muscle relaxation ( J:131302 )

• within 2 weeks of treatment with doxycycline, mice develop myotonia

cardiovascular system

abnormal atrioventricular node conduction ( J:131302 )

• within 2 weeks of treatment with doxycycline, mice develop progressive heart block

Genotype
MGI:3851519

cx75

• 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

Genotype
MGI:5141005

cx76

• Allelic Composition: Cdc42^tm1.1Yizh/Cdc42⁺; Nkx2-5^tm1Siz/Nkx2-5⁺
• Genetic Background: involves: 129S4/SvJaeSor

cardiovascular system

decreased cardiac output ( J:174208 )

• at 4 weeks of age

decreased cardiac stroke volume ( J:174208 )

• at 4 weeks of age, mice exhibit decreased cardiac stroke volume compared with wild-type mice and single heterozygotes

decreased heart ventricle muscle contractility ( J:174208 )

• at 4 weeks of age, mice exhibit decreased cardiac function (reduced left ventricle ejection fraction, fractional shortening of the ventricular chamber, volume of ejected blood with each heart beat, and cardiac output) compared with wild-type mice or single heterozygotes

prolonged P wave ( J:174208 )

prolonged QRS complex duration ( J:174208 )

prolonged QT interval ( J:174208 )

• mice exhibit prolonged QT and QTc intervals compared with wild-type mice

muscle

decreased heart ventricle muscle contractility ( J:174208 )

• at 4 weeks of age, mice exhibit decreased cardiac function (reduced left ventricle ejection fraction, fractional shortening of the ventricular chamber, volume of ejected blood with each heart beat, and cardiac output) compared with wild-type mice or single heterozygotes

Genotype
MGI:3607708

cx77

• Allelic Composition: Hand2^tm1Dsr/Hand2⁺; Nkx2-5^tm1Wehi/Nkx2-5⁺
• Genetic Background: involves: C57BL/6

mortality/aging

mortality/aging ( J:72600 )

N • double heterozygotes are viable, fertile, and grow normally exhibiting a normal lifespan

Genotype
MGI:3716381

cx78

• Allelic Composition: Nkx2-5^tm3Rph/Nkx2-5⁺; Tbx20^tm1.1Rph/Tbx20⁺
• Genetic Background: involves: C57BL/6

cardiovascular system

dilated heart right ventricle ( J:98489 )

cardiac fibrosis ( J:98489 )

Genotype
MGI:6360225

cx79

• Allelic Composition: Mrtfb^em1Dsr/Mrtfb⁺; Myh7^em1Dsr/Myh7⁺; Nkx2-5^em1Dsr/Nkx2-5⁺
• Genetic Background: involves: C57BL/6J

cardiovascular system

abnormal trabecula carnea morphology ( J:277399 )

• mice exhibit deep trabeculations in the left ventricular wall at P3

• mice show a significant difference in trabecular complexity compared to controls

thin ventricular wall ( J:277399 )

• decrease in the apical wall thickness

• however, no changes in left ventricular free wall thickness

increased response of heart to induced stress ( J:277399 )

• mice exhibit a reduction in cardiac function after transverse aortic constriction compared to wild-type mice, with incomplete penetrance

• however, cardiac function by echocardiography is normal at baseline in adult mice

homeostasis/metabolism

increased response of heart to induced stress ( J:277399 )

• mice exhibit a reduction in cardiac function after transverse aortic constriction compared to wild-type mice, with incomplete penetrance

• however, cardiac function by echocardiography is normal at baseline in adult mice

muscle

abnormal trabecula carnea morphology ( J:277399 )

• mice exhibit deep trabeculations in the left ventricular wall at P3

• mice show a significant difference in trabecular complexity compared to controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
left ventricular noncompaction		DOID:0060480	OMIM:604169	J:277399