Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/100170
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Type: Journal article
Title: Pcdh19 loss-of-function increases neuronal migration in vitro but is dispensable for brain development in mice
Author: Pederick, D.
Homan, C.
Jaehne, E.
Piltz, S.
Haines, B.
Baune, B.
Jolly, L.
Hughes, J.
Gecz, J.
Thomas, P.
Citation: Scientific Reports, 2016; 6(1):26765-1-26765-10
Publisher: Nature Publishing
Issue Date: 2016
ISSN: 2045-2322
2045-2322
Statement of
Responsibility: 
Daniel T. Pederick, Claire C. Homan, Emily J. Jaehne, Sandra G. Piltz, Bryan P. Haines, Bernhard T. Baune, Lachlan A. Jolly, James N. Hughes, Jozef Gecz, Paul Q. Thomas
Abstract: Protocadherin 19 (Pcdh19) is an X-linked gene belonging to the protocadherin superfamily, whose members are predominantly expressed in the central nervous system and have been implicated in cell-cell adhesion, axon guidance and dendrite self-avoidance. Heterozygous loss-of-function mutations in humans result in the childhood epilepsy disorder PCDH19 Girls Clustering Epilepsy (PCDH19 GCE) indicating that PCDH19 is required for brain development. However, understanding PCDH19 function in vivo has proven challenging and has not been studied in mammalian models. Here, we validate a murine Pcdh19 null allele in which a β-Geo reporter cassette is expressed under the control of the endogenous promoter. Analysis of β-Geo reporter activity revealed widespread but restricted expression of PCDH19 in embryonic, postnatal and adult brains. No gross morphological defects were identified in Pcdh19(+/β-Geo) and Pcdh19(Y/β-Geo) brains and the location of Pcdh19 null cells was normal. However, in vitro migration assays revealed that the motility of Pcdh19 null neurons was significantly elevated, potentially contributing to pathogenesis in patients with PCDH19 mutations. Overall our initial characterization of Pcdh19(+/β-Geo), Pcdh19(β-Geo/β-Geo) and Pcdh19(Y/β-Geo)mice reveals that despite widespread expression of Pcdh19 in the CNS, and its role in human epilepsy, its function in mice is not essential for brain development.
Keywords: Brain; Hippocampus; Neurons; Synapses; Cells, Cultured; Animals; Mice, Knockout; Humans; Mice; Epilepsy; Cadherins; Cell Movement; Genotype; Phenotype; Female; Male; Neural Stem Cells
Rights: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
RMID: 0030048617
DOI: 10.1038/srep26765
Appears in Collections:Medicine publications

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