A New Targeted Transgenic Mouse Line for the Study of Protocadherin <scp>γC4</scp>

The γ-protocadherins (γ-Pcdhs) comprise 22 homophilic cell adhesion molecule isoforms, expressed from the Pcdhg gene cluster via promoter choice mechanisms that serve many crucial functions during neural development. Emerging evidence supports the hypothesis that distinct isoforms have unique functions. The γC4 isoform, which is expressed from the Pcdhgc4 promoter and includes its unique variable exon, is the sole γ-Pcdh isoform essential for the postnatal survival in mice. Here we describe a new mouse line (C4-GFP) in which Pcdhgc4 with a C-terminal GFP tag is expressed from the Rosa26 locus following excision of a lox-Stop-lox cassette by Cre recombinase. We report that restricted expression of this transgene in the nervous system using Nestin-Cre is sufficient to rescue the neonatal lethality of mice mutant for Pcdhgc4. This new line will be a vital tool for dissecting mechanisms underlying the functions of this essential cell adhesion molecule gene, mutations in which have been associated with neurodevelopmental disorders in humans.