Table 1.
Range of Congenital Defects Observed in the Conditional Slit and Robo Lines
| Congenital defect | Wild type |
Robo1−/− ; Robo2fl/fl (Domyan et al, 5 Dev Cell. 2013) |
Robo4fl/fl (Zheng et al, 8 2012) |
Slit2fl /fl |
Slit3fl/fl | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| E18.5 | E18.5 | E18.5 | P0 | E18.5 | ||||||
| No cre | Nkx2.5‐cre (Moses et al, 9 2001) | Tie2‐cre (Koni et al, 11 2001) | Wnt1‐cre (Danielian et al, 10 1998) | Tie2‐cre (Koni et al, 11 2001) | Tie2‐cre (Koni et al, 11 2001) | Wnt1‐cre (Danielian et al, 10 1998) | Tie2‐cre (Koni et al, 11 2001) | Myh11‐creERT2 (Wirth et al, 12 2008) | ||
| Full Robo1−/− | All cardiac tissues including second heart field and excluding neural crest | Endocardium, endocardially derived tissues | Neural crest | Endocardium, endocardially derived tissues | Endocardium, endocardially derived tissues | Neural crest | Endocardium, endocardially derived tissues | Smooth muscle | ||
| Ventricular septal defect—membranous | 0% (0/35) | 11% (1/9) | 33% (2/6) | 20% (1/5) | 17% (1/6) | 0% (0/6) | 0% (0/5) | 0% (0/5) | 17% (1/6) | 17% (1/6) |
| Ventricular septal defect—muscular | 6% (2/35) | 11% (1/9) | 17% (1/6) | 20% (1/5) | 0% (0/6) | 0% (0/6) | 20% (1/5) | 0% (0/5) | 0% (0/6) | 0% (0/6) |
| Atrial septal defect | 0% (0/33) | 11% (1/9) | 0% (0/6) | 0% (0/5) | 0% (0/6) | 0% (0/6) | 0% (0/5) | 0% (0/5) | 0% (0/5) | 20% (1/5) |
| Bicuspid aortic valves | 0% (0/36) | 11% (1/9)* 1/9 | 17% (1/6)* 1/6 | 40% (2/5) ‡ 1 /5 † 1/5 | 100% (6/6)* 4/6 † 1/6 ‡ 1/6 § | 17% (1/6) | 20% (1/5)* 1/5 | 0% (0/5) | 100% (6/6) ‡ 6/6 § | 50% (3/6) ‡ 1/6 † 2/6 § |
| Bicuspid pulmonary valves | 0% (0/35) | 0% (0/9) | 0% (0/6) | 20% (1/5) | 33% (2/6) | 0% (0/5) | 0% (0/5) | 0% (0/5) | 17% (1/6) | 17% (1/6) |
| Immature aortic valves ¶ | 0% (0/36) | 33% (3/9) | 67% (4/6) | 60% (3/5) | 100% (5/5) | 0% (0/6) | 20% (1/5) | 20% (1/5) | 100% (5/5) | 33% (2/6) |
| Immature pulmonary valves ¶ | 0% (0/36) | 22% (2/9) | 33% (2/6) | 40% (2/5) | 40% (2/5) | 0% (0/6) | 0% (0/5) | 20% (1/5) | 60% (3/5) | 67% (4/6) |
| Left persistent inferior caval vein | 0% (0/36) | 0% (0/9) | 0% (0/6) | 0% (0/5) | 0% (0/6) | 0% (0/6) | 0% (0/5) | 0% (0/5) | 100% (6/6) | 20% (1/5) |
| Absent left superior caval vein | 0% (0/36) | 0% (0/9) | 0% (0/6) | 0% (0/5) | 0% (0/6) | 0% (0/6) | 0% (0/5) | 0% (0/5) | 0% (0/6) | 50% (3/6) |
| Pericardial defect | 0% (0/36) | 11% (1/9) | 0% (0/6) | 0% (0/5) | 0% (0/6) | 0% (0/6) | 0% (0/5) | 0% (0/5) | 0% (0/6) | 0% (0/6) |
| Diaphragmatic hernia | 3% (1/36) | 0% (0/9) | 33% (2/6) | 0% (0/5) | 0% (0/6) | 0% (0/6) | 0% (0/5) | 0% (0/5) | 100% (6/6) | 83% (5/6) |
E indicates embryonic day, P indicates postnatal day. Slashed data in parentheses indicate the number affected hearts of the total analyzed. Robo, Roundabout Guidance Receptor. Slit, Slit Guidance Ligand. Nkx2.5, NK2 Homeobox 5. Wnt1, Wnt Family Member 1. Tie2/Tek, TEK Receptor Tyrosine Kinase. Myh11, Myosin Heavy Chain 11.
Bicuspid aortic valve subtype: bicuspid valves without visible raphe—noncoronary leaflet missing.
Bicuspid aortic valve subtype: bicuspid vales with visible raphe—fusion of left and noncoronary leaflets.
Bicuspid aortic valve subtype: bicuspid vales with visible raphe—fusion of right and noncoronary leaflets.
Indication of interaction between endocardial SLIT3 and neural crest ROBO2 for bicuspid aortic valves.
Defined as average valve size at least 25% larger than the average littermate wild‐type valve size.