| First Author | Garrett AM | Year | 2019 |
| Journal | PLoS Genet | Volume | 15 |
| Issue | 12 | Pages | e1008554 |
| PubMed ID | 31877124 | Mgi Jnum | J:285314 |
| Mgi Id | MGI:6386647 | Doi | 10.1371/journal.pgen.1008554 |
| Citation | Garrett AM, et al. (2019) CRISPR/Cas9 interrogation of the mouse Pcdhg gene cluster reveals a crucial isoform-specific role for Pcdhgc4. PLoS Genet 15(12):e1008554 |
| abstractText | The mammalian Pcdhg gene cluster encodes a family of 22 cell adhesion molecules, the gamma-Protocadherins (gamma-Pcdhs), critical for neuronal survival and neural circuit formation. The extent to which isoform diversity-a gamma-Pcdh hallmark-is required for their functions remains unclear. We used a CRISPR/Cas9 approach to reduce isoform diversity, targeting each Pcdhg variable exon with pooled sgRNAs to generate an allelic series of 26 mouse lines with 1 to 21 isoforms disrupted via discrete indels at guide sites and/or larger deletions/rearrangements. Analysis of 5 mutant lines indicates that postnatal viability and neuronal survival do not require isoform diversity. Surprisingly, given reports that it might not independently engage in trans-interactions, we find that gammaC4, encoded by Pcdhgc4, is the only critical isoform. Because the human orthologue is the only PCDHG gene constrained in humans, our results indicate a conserved gammaC4 function that likely involves distinct molecular mechanisms. |
