title: A Disc1 mutation differentially affects neurites and spines in hippocampal and cortical neurons.
abstract: A balanced chromosomal translocation segregating with schizophrenia and affective disorders in a large Scottish family disrupting DISC1 implicated this gene as a susceptibility gene for major mental illness. Here we study neurons derived from a genetically engineered mouse strain with a truncating lesion disrupting the endogenous Disc1 ortholog. We provide a detailed account of the consequences of this mutation on axonal and dendritic morphogenesis as well as dendritic spine development in cultured hippocampal and cortical neurons. We show that the mutation has distinct effects on these two types of neurons, supporting a cell-type specific role of Disc1 in establishing structural connections among neurons. Moreover, using a validated antibody we provide evidence indicating that Disc1 localizes primarily to Golgi apparatus-related vesicles. Our results support the notion that in vitro cultures derived from Disc1(Tm1Kara) mice provide a valuable model for future mechanistic analysis of the cellular and biochemical effects of this mutation, and can thus serve as a platform for drug discovery efforts.
authors: Department of Physiology and Cellular Biophysics, Columbia University, 630 West, 168th Street, New York, NY 10032, USA.
authors: A M
authors: AM
authors: Lepagnol-Bestel
authors: M
authors: M
authors: Kvajo
authors: M
authors: M
authors: Karayiorgou
authors: M
authors: M
authors: Simonneau
authors: J A
authors: JA
authors: Gogos
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000378:metabolism; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D049229:Dendritic Spines / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D016501:Neurites / Q000378:metabolism*; D055495:Neurogenesis; D009928:Organ Specificity; D021381:Protein Transport
chemical_list: C498794:Disc1 protein, mouse; D009419:Nerve Tissue Proteins
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