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A new mouse mutant with a discrete mutation in Pcdhgc5 reveals that the Protocadherin gC5 isoform is not essential for dendrite arborization in the cerebral cortex

ABSTRACT: There are ~60 clustered protocadherin (cPcdh) isoforms expressed from three gene clusters (Pcdha, Pcdhb, Pcdhg) arrayed in tandem across nearly 1 Mb in mammals. cPcdhs are homophilic cell adhesion molecules (CAMs) critical for a host of neural developmental functions consistent with a role in cell-cell recognition. Indeed, isoforms make recognition modules in combination to generate recognition diversity far exceeding the ~60 individual CAMs. However, there is also growing evidence for specialized functions for specific isoforms, particularly the C-type isoforms found at the 3’ ends of the Pcdha cluster (aC1 and aC2) and at the 3’ end of the Pcdhg cluster (gC3, gC4, and gC5). We have previously described unique roles for gC3 in dendrite arborization in the cerebral cortex and neural circuit formation in the spinal cord, as well as for gC4 in neuronal survival. Here we report a new mouse mutant specifically targeting the Pcdhgc5 exon encoding gC5. Unlike the rest of the Pcdhg cluster, expression of this isoform does not begin until postnatal stages of mouse development, increasing in the second week of life, suggesting specialized roles. We found significant expression changes in gene pathways involved in synaptic activity, learning and memory, and cognition. Despite this, we saw no major disruption in the cerebral cortex in neuronal organization, survival, dendritic arborization, or synaptic protein expression in these mutants. This new model will be an important tool for future studies delineating specific functions for gC5.

ORGANISM(S): Mus musculus

PROVIDER: GSE310953 | GEO | 2026/01/28

REPOSITORIES: GEO

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