October 29, 2020

Cellular and behavioral characterization of Pcdh19 mutant mice: subtle molecular changes, increased exploratory behavior and an impact of social environment.

Mutations in the X-linked cell adhesion protein PCDH19 lead to seizures, cognitive impairment and other behavioral comorbidities when present in a mosaic pattern. Neither the molecular mechanisms underpinning this disorder, nor the function of PCDH19 itself are well understood. By combining RNA in situ hybridization with immunohistochemistry and analyzing single cell RNAseq datasets, we provide a first account of the subtypes of neurons expressing Pcdh19/PCDH19, both in the mouse and the human cortex. Our quantitative analysis of the Pcdh19 mutant mouse reveals subtle changes in cortical layer composition, with no major alterations of the main axonal tracts. However, Pcdh19 mutant animals, particularly females, display preweaning behavioral changes, including reduced anxiety and increased exploratory behavior. Our experiments also reveal an effect of the social environment on the behavior of wild-type littermates of Pcdh19 mutant mice when compared with wild-type animals not housed with mutants. This is a second case of a mutated X-linked gene encoding a membrane protein expressed in the developing cortex impacting the behavior of co-housed wild-type littermates.

 bioRxiv Subject Collection: Neuroscience

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