Reduced NMDAR1 expression in the Sp4 hypomorphic mouse may contribute to endophenotypes of human psychiatric disorders.

Human Molecular Genetics
Xianjin ZhouMark A Geyer

Abstract

The reduced expression of the Sp4 gene in Sp4 hypomorphic mice resulted in subtle vacuolization in the hippocampus as well as deficits in sensorimotor gating and contextual memory, putative endophenotypes for schizophrenia and other psychiatric disorders. In this study, we examined both spatial learning/memory and hippocampal long-term potentiation (LTP) of Sp4 hypomorphic mice. Impaired spatial learning/memory and markedly reduced LTP were found. To corroborate the functional studies, the expression of N-methyl-D-aspartate (NMDA) glutamate receptors was investigated with both western blot and immunohistochemical analyses. The reduced expression of the Sp4 gene decreased the level of the NR1 subunit of NMDA receptors in Sp4 hypomorphic mice. In human, SP4 gene was found to be deleted sporadically in schizophrenia patients, corroborating evidence that polymorphisms of human SP4 gene are associated with schizophrenia and other psychiatric disorders. Impaired NMDA neurotransmission has been implicated in several human psychiatric disorders. As yet, it remains unclear how mutations of candidate susceptibility genes for these disorders may contribute to the disruption of NMDA neurotransmission. Sp4 hypomorphic mice could therefore s...Continue Reading

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Citations

Sep 2, 2014·Journal of Psychiatric Research·Raquel PinachoBelén Ramos
Oct 16, 2015·Biochimica Et Biophysica Acta·Bindu NairMargaret T T Wong-Riley
Jan 31, 2014·Journal of Neurochemistry·Gregory SaiaGrace Gill
Apr 25, 2015·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Jared W YoungXianjin Zhou
Jun 8, 2015·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Raquel PinachoBelén Ramos
Jun 4, 2015·The International Journal of Neuropsychopharmacology·Kerin K HigaXianjin Zhou
Oct 10, 2015·The British Journal of Psychiatry : the Journal of Mental Science·Jianhua ChenYongyong Shi
Nov 7, 2015·The British Journal of Psychiatry : the Journal of Mental Science·Montserrat FustéBelén Ramos
Jun 7, 2017·Schizophrenia Bulletin·Samuel A BarnesJared W Young
Jul 2, 2017·British Journal of Pharmacology·Colm M P O'TuathaighJohn L Waddington
Jul 25, 2017·Cellular and Molecular Life Sciences : CMLS·Fernanda Ledda, Gustavo Paratcha
Nov 19, 2015·Frontiers in Cellular Neuroscience·Agnese De MarioAlessandro Bertoli
Dec 17, 2015·Genes, Brain, and Behavior·Zackary A CopeJared W Young

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