Figure 5. Murine Models of Atrioventricular Septal Defect.

Figures 5A– D′ depict Pitx2c^−/− specimens and wild-type controls. At 12ED in a normal mouse heart (5A), the septum primum with its mesenchymal cap can be seen protruding toward the endocardial cushions. At this stage, both the ostium primum and secundum are patent but the ostium primum is in the process of closing. In Pitx2c^−/− specimens at 12ED (5B), however, no septum primum is observed and as such, the atria communicate freely. By 15ED in the normal mouse (5C, C′), the ostium primum has fully closed while the ostium secundum is patent. The right and left venous valves, which demarcate the orifice of systemic venous return, can be observed within the right atrium. In the Pitx2c^−/− specimen at 15ED (5D, D′), the septum primum is absent and, consistent with right atrial isomerism, two sets of venous valves (one in each atrium) can be observed. In this model of AVSD, an ostium primum enables atrial shunting while a ventricular septal defect permits shunting at the ventricular level as well (5D, D′).

Figures 5E– H′ depict deletion of Smoothened from the anterior heart field, including the DMP, (Mef2c-AHF-cre; Smo^f/f) (5F, 5H, 5H′) and wild-type controls (Smo^f/f) (5E, 5G, 5G′). Here, at 13ED, the septum primum may be observed within the conditional knockout (5F); however, the ostium primum is still patent and the ostium secundum has not formed. Even two days later in developent, the primary septum is still attached to the roof of the atria and a large ostium primum defect can be observed in these mutants (5H, H′). MC, mesenchymal cap; SP, septum primum; SS, septum secundum; OP, ostium primum; OS, ostium secundum; iAVC, inferior atrioventricular cushion; sAVC, superior atrioventricular cushion; AVSD, atrioventricular septal defect