et al., 2001). These 5 Pcdh genes (Pcdhac1, Pcdhac2, Pcdhgc3, Pcdhgc4, and Pcdhgc5) are designated C-type genes, to be distinguished from A-type and B-type genes of the Pcdhg cluster. The C-type isoforms bear several unique features among all Pcdhs: 1) While all other Pcdhs are more closely related to members within their own cluster, C-type isoforms are evolutionarily divergent, forming a separate branch in the phylogenetic tree (Wu and Maniatis, 1999; Wu et al., 2001); 2) Three out of the five C-type genes (Pcdhac2, Pcdhgc4 and Pcdhgc5) lack the conserved sequence element (CSE) found in the promoters of all other Pcdh genes (except Pcdhb1), suggesting that these genes are regulated differently (Wu et al., 2001). 3) Single cell RT-PCR experiments indicated that, while other Pcdh genes are stochastically and monoallelically expressed in Purkinje neurons, every neuron expresses all five C-type genes from both chromosomes (Esumi et al., 2005; Kaneko et al., 2006). Taken together, these observations suggest that the C-type isoforms play unique and essential roles among all clustered Pcdhs. To investigate this possibility, we generated mutant mice lacking the 3 C-type genes (Pcdhgc3, Pcdhgc4, Pcdhgc5) in the Pcdhg cluster.
