%0 Journal Article
%T Sex-Specific Proteomic Changes Induced by Genetic Deletion of Fibroblast Growth Factor 14 (FGF14), a Regulator of Neuronal Ion Channels
%A Alexander S. Shavkunov
%A Cheryl Lichti
%A Fernanda Laezza
%A Jessica Di Re
%A Kangling Zhang
%A Mark L. Sowers
%A Paul A. Wadsworth
%J -
%D 2019
%R https://doi.org/10.3390/proteomes7010005
%X Abstract Fibroblast growth factor 14 (FGF14) is a member of the intracellular FGFs, which is a group of proteins involved in neuronal ion channel regulation and synaptic transmission. We previously demonstrated that male Fgf14£¿/£¿ mice recapitulate the salient endophenotypes of synaptic dysfunction and behaviors that are associated with schizophrenia (SZ). As the underlying etiology of SZ and its sex-specific onset remain elusive, the Fgf14£¿/£¿ model may provide a valuable tool to interrogate pathways related to disease mechanisms. Here, we performed label-free quantitative proteomics to identify enriched pathways in both male and female hippocampi from Fgf14+/+ and Fgf14£¿/£¿ mice. We discovered that all of the differentially expressed proteins measured in Fgf14£¿/£¿ animals, relative to their same-sex wildtype counterparts, are associated with SZ based on genome-wide association data. In addition, measured changes in the proteome were predominantly sex-specific, with the male Fgf14£¿/£¿ mice distinctly enriched for pathways associated with neuropsychiatric disorders. In the male Fgf14£¿/£¿ mouse, we found molecular characteristics that, in part, may explain a previously described neurotransmission and behavioral phenotype. This includes decreased levels of ALDH1A1 and protein kinase A (PRKAR2B). ALDH1A1 has been shown to mediate an alternative pathway for gamma-aminobutyric acid (GABA) synthesis, while PRKAR2B is essential for dopamine 2 receptor signaling, which is the basis of current antipsychotics. Collectively, our results provide new insights in the role of FGF14 and support the use of the Fgf14£¿/£¿ mouse as a useful preclinical model of SZ for generating hypotheses on disease mechanisms, sex-specific manifestation, and therapy. View Full-Tex
%K mass spectroscopy
%K bioinformatics
%K FGF14
%K voltage gated channels
%K schizophrenia
%K autism
%K Alzheimer¡¯s Disease
%K sex-specific differences
%K synaptic plasticity
%K cognitive impairment
%K excitatory/inhibitory tone
%U https://www.mdpi.com/2227-7382/7/1/5