Table 2.

Semaphorin receptor mutants with cardiovascular defects

Mutation(s)	Receptors or Ligands	Stage of lethality	Cardiovascular phenotypes and functions	Refs.
Plexins
Plxna1 −/−	Sema3a, Sema5a or 5b, Sema6c or 6d	Viable	No obvious cardiac defects. Lymphatic valves are abnormal.	(Bouvree et al., 2012; Takegahara et al., 2006)
Plxna2 −/−	Sema6a or 6b	Viable	PTA and lack of aortic and pulmonary channel septation with incomplete penetrance. Double knockouts lacking Plxna2 and Plxna4 exhibit cardiovascular defects with higher penetrance.	(Suto et al., 2007; Toyofuku et al., 2008)
Plxna4 −/−	Sema6a or 6b	Viable	Double knockouts lacking Plxna2 and Plxna4 exhibit cardiovascular defects with higher penetrance.	(Toyofuku et al., 2008)
Plxnd1−/− and Plxnd1ecKO	Sema3a, 3c (neuropilin dependent) Sema3e, 4a (neuropilin-independent)	Postnatal	PTA, VSD, atrial defects, coronary artery and aortic arch defects.	(Gitler et al., 2004; Zhang et al., 2009)
Neuropilins
Nrp1 −/− Nrp1 ecKO Nrp1 −Sema	Coreceptor for class 3 semaphorins and others	Embryonic E10.5-12.5 Perinatal Postnatal	Various cardiac and vascular defects including PTA and aortic arch defects. PTA, BAE, AOC, VSD. BAE, VSD, lymphatic vessels and valve defects.	(Gu et al., 2003; Kawasaki et al., 1999)
Nrp2 −/−	Coreceptor for class 3 semaphorins and others	Viable	Lymphatic vessel and capillary formation defect.	(Giger et al., 2000; Yuan et al., 2002)
Nrp1−/−; Nrp2−/−	Coreceptor for class 3 semaphorins and others	Embryonic (~E8.0)	Vascular anomalies in both embryos and placenta.	(Takashima et al., 2002)
Nrp1Sema-; Nrp2−/−	Coreceptor for class 3 semaphorins and others	Not reported	PTA, BAE, AOC and VSD, no vascular defects reported.	(Gu et al., 2003)

BAE, Bilateral atrial enlargement; AOC, anomalous origin of the coronary arteries; VSD, ventricular septal defect; PTA, persistent truncus arteriosus.