The most remarkable difference between the two types of mutants is that, the neonatal lethality of C-type isoform knockouts can be rescued by genetically blocking apoptosis, while that of the full cluster Pcdhg deletion mutants cannot be rescued. The persistence of neonatal lethality in Pcdhgdel/del;Bax−/− mutants reveals an additional, independent role of Pcdhg isoforms that is required for postnatal development. Therefore, the role of Pcdhg cluster in neuronal survival is primarily, if not specifically mediated by the C-type isoforms, whereas the requirement of Pcdhg cluster for postnatal development appears to be the collective function of all 22 isoforms in neuronal wiring. Indeed, in a parallel study, we have found dendritic arborization defects in Pcdhg null mutants that are not observed in the C-type isoform knockouts (Lefebvre et al., 2012). Hence similar phenotypes are observed in the Pcdhgtcko/tcko and Pcdhgdel/del mutants because the C-type genes are deleted in both lines, and the resulting neuronal cell loss dominates the phenotypes. In the absence of apoptosis, however, the neonatal lethality in C-type isoform knockouts is rescued since neural circuitries essential for postnatal survival
