Maltesh Kambali, Yan Li, Petr Unichenko, Jessica Feria Pliego, Rachita Yadav, Jing Liu, Patrick McGuinness, Johanna G Cobb, Muxiao Wang, Rajasekar Nagarajan, Jinrui Lyu, Vanessa Vongsouthi, Colin J Jackson, Elif Engin, Joseph T Coyle, Jeaweon Shin, Michael E Talkowski, Gregg E Homanics, Vadim Y Bolshakov, Christian Henneberger, Uwe Rudolph
The biological significance of a small supernumerary marker chromosome that results in dosage alterations to chromosome 9p24.1, including triplication of the GLDC gene encoding glycine decarboxylase, in two patients with psychosis is unclear. In an allelic series of copy number variant mouse models, we identify that triplication of Gldc reduces extracellular glycine levels as determined by optical fluorescence resonance energy transfer (FRET) in dentate gyrus (DG) but not in CA1, suppresses long-term potentiation (LTP) in mPP-DG synapses but not in CA3-CA1 synapses, reduces the activity of biochemical pathways implicated in schizophrenia and mitochondrial bioenergetics, and displays deficits in prepulse inhibition, startle habituation, latent inhibition, working memory, sociability and social preference...
May 29, 2023: bioRxiv