Table 1.
Murine models of congenital heart disease (CHD)
| Gene | OMIM # | Human CHD phenotype | Syndrome with associated CHD | Mouse genotype | Mouse phenotype | References |
|---|---|---|---|---|---|---|
| Cardiac septation defects | ||||||
| ACVR1 (ALK2) | 102576 | AVSD | Alk2fl/−; Tie2-Cre | AVSD, VSD | Wang et al. 2005 | |
| CITED2 | 602937 | ASD, VSD | Cited2−/− | ASD, VSD, DORV, TA | Bamforth et al. 2001 | |
| CREBBP | 600140 | ASD, VSD, CoA, PS, BAV | Rubinstein–Taybi syndrome | CBP+/− | ASD, VSD, BAV | Oike et al. 1999 |
| EP300 | 602700 | ASD, VSD, CoA, PS, BAV | Rubinstein–Taybi syndrome | EP300+/AS | ASD, VSD | Shikama et al. 2003 |
| GATA4 | 600576 | ASD, PS, TOF, VSD, AVSD | Gata4Δex2/wt | ASD, VSD, AVSD | Rajagopal et al. 2007 | |
| Gata4G295Ski/wt | ASD, AS, PS | Misra et al. 2012; LaHaye et al. 2019 | ||||
| KMT2D | 602113 | AS, CoA, ASD, VSD, BAV, HLHS, TOF | Kabuki syndrome | Kmt2dfl/fl; Mef2c-AHF-Cre | VSD | Ang et al. 2016a |
| NIPBL | 608667 | ASD, VSD, PS | Comelia de Lange syndrome | Nipbl+/− | ASD, VSD | Kawauchi et al. 2009 |
| NKX2-5 | 600584 | ASD, atrioventricular conduction delay, TOF, VSD, HLHS | Nkx2 5+/− | ASD, PFO, VSD, AVSD, BAV, AS | Biben et al. 2000; Winston et al. 2010 | |
| Nkx2.5+/R52G | ASD, VSD, AVSD, Ebstein's anomaly, atrioventricular block, tricuspid valve atresia | Ashraf et al. 2014; Chowdhury et al. 2015 | ||||
| Nkx2.5R141C/+ | ASD, atrioventricular block, VSD | Zakariyah et al. 2017 | ||||
| PTPN11 | 176876 | PS, AVSD, CoA, ASD, VSD, TOF, left ventricular outflow tract obstruction | Noonan syndrome | Ptpn11D61G/+ | ASD, AVSD, DORV | Araki et al. 2004 |
| SHOC2 | 602775 | PS, AVSD, CoA, ASD, VSD, TOF | Noonan syndrome | Sur-8Δ/fl; Tie2-Cre | VSD, DORV, TGA | Yi et al. 2010 |
| TBX5 | 601620 | ASD, VSD | Holt–Oram syndrome | Tbx5del/+ | ASD, atrioventricular block, VSD | Bruneau et al. 2001 |
| Tbx5flox/flox; Tie2-Cre | ASD, PFO | Nadeau et al. 2010 | ||||
| 190685 | ASD, VSD, AVSD, TOF | Down syndrome | Tc1 | VSD, AVSD | O'Doherty et al. 2005 | |
| Dp(10)1Yey/+;Dp(16)1Yey/+;Dp(17)1Yey/+ | VSD, AVSD | Yu et al. 2010 | ||||
|
Dp1Tyb Dp3Tyb |
VSD, AVSD, DORV | Lana-Elola et al. 2016 | ||||
| Cardiac valve malformations | ||||||
| DCHS1 | 603057 | MVP | Dchs1+/− | MVP | Durst et al. 2015 | |
| GATA5 | 611496 | BAV |
Gata5−/− Gata5fl/fl; Tie2-Cre |
BAV, AS | Laforest et al. 2011 | |
| GATA6 | 601656 | TA, ASD, AVSD, TOF, BAV |
Gata6+/− Gata6wt/fl; Isl1-Cre |
BAV | Gharibeh et al. 2018 | |
| MATR3 | 164015 | BAV, CoA, PDA | Matr3+/− | BAV, CoA, PDA, VSD, DORV | Quintero-Rivera et al. 2015 | |
| NOTCH1 | 190198 | BAV, AS, HLHS, TOF, PS, CAVD | Notch1+/− | BAV, CAVD, aortic aneurysm | Nigam and Srivastava 2009; Nus et al. 2011; Bosse et al. 2013; Koenig et al. 2017 | |
| Notch1fl/fl; Nfatc1-enCre | BAV | MacGrogan et al. 2016; Wang et al. 2017 | ||||
| Notch1+/− mTRG2 | CAVD, AS | Theodoris et al. 2017 | ||||
| Nos3−/−; Notch1+/− | BAV, AS, AR, CAVD, TOF | Bosse et al. 2013; Koenig et al. 2016 | ||||
| SMAD6 | 602931 | BAV, AS, CoA | Smad6−/− | Cardiac valve hyperplasia | Galvin et al. 2000 | |
| Conotruncal and aortic arch artery defects | ||||||
| CHD7 | 608892 | TOF, DORV, VSD, ASD, TA, PS, AS, MS, TS | CHARGE syndrome | Chd7+/− | IAA, aortic arch defects | Randall et al. 2009 |
| CRKL | 602007 | TOF, TA, IAA, VSD, aortic arch defects | 22q11 deletion syndrome | Crkol−/− | IAA, VSD, overriding aorta, DORV | Guris et al. 2001 |
| FOXC1 | 601090 | TOF | Foxc1−/− | CoA, semilunar valve dysplasia, IAA, VSD | Winnier et al. 1999 | |
| FOXC2 | 602402 | TOF | Foxc2−/− | IAA, VSD | Winnier et al. 1999 | |
| FOXH1 | 603621 | TOF, VSD | Foxh1C/− | Right isomerism, ASD, VSD, TGA, DORV | Yamamoto et al. 2003 | |
| JAG1 | 601920 | TOF, PS, ASD, VSD | Allagille syndrome |
Jag1fl/fl; Islet1-Cre Jag1fl/fl; Mef2c-AHF-Cre |
DORV, PS, TA, ASD, VSD, aortic arch defects | High et al. 2009 |
| TBX1 | 602054 | TOF, TA, IAA, VSD, aortic arch defects | 22q11 deletion syndrome | Df1/+ | aortic arch defects, VSD | Lindsay et al. 1999 |
| Tbx1Neo2/Neo | TOF, TA, DORV, IAA, VSD, aortic arch defects | Zhang and Baldini 2008 | ||||
| Tbx1neo/neo | TA, IAA, VSD, aortic arch defects | Hu et al. 2004 | ||||
| Tbx1+/− | IAA, aortic arch defects | Lindsay et al. 2001; Zhang et al. 2005 | ||||
| ZFPM2(FOG2) | 603693 | TOF, DORV | Fog2−/− | TOF, ASD, VSD | Tevosian et al. 2000; Pizzuti et al. 2003 | |
| Other cardiac defects | ||||||
| ELN | 130160 | SVAS | Williams–Beuren syndrome | Eln+/− | SVAS | Li et al. 1998 |
| FBN1 | 134797 | BAV, AR, MVP, aortic aneurysm, aortic dissection | Marfan syndrome | Fbn1C1039G/+ | MVP, aortic aneurysm | Ng et al. 2004; Habashi et al. 2006 |
(AS) aortic valve stenosis, (ASD) atrial septal defect, (AR) aortic valve regurgitation, (AVSD) atrioventricular septal defect, (BAV) bicuspid aortic valve, (CAVD) calcific aortic valve disease, (CoA) coarctation of aorta, (DORV) double-outlet right ventricle, (HLHS) hypoplastic left heart syndrome, (IAA) interrupted aortic arch, (MS) mitral valve stenosis, (MVP) mitral valve prolapse, (PDA) patent ductus arteriosus, (PFO) patent foremen ovale, (PS) pulmonic valve stenosis, (SVAS) supravalvar aortic stenosis, (TA) truncus arteriosus, (TGA) transposition of great arteries, (TOF) tetralogy of Fallot, (TS) tricuspid valve stenosis, (VSD) ventricular septal defect.