title: Disc1 variation leads to specific alterations in adult neurogenesis.
abstract: Disrupted in schizophrenia 1 (DISC1) is a risk factor for a spectrum of neuropsychiatric illnesses including schizophrenia, bipolar disorder, and major depressive disorder. Here we use two missense Disc1 mouse mutants, described previously with distinct behavioural phenotypes, to demonstrate that Disc1 variation exerts differing effects on the formation of newly generated neurons in the adult hippocampus. Disc1 mice carrying a homozygous Q31L mutation, and displaying depressive-like phenotypes, have fewer proliferating cells while Disc1 mice with a homozygous L100P mutation that induces schizophrenia-like phenotypes, show changes in the generation, placement and maturation of newly generated neurons in the hippocampal dentate gyrus. Our results demonstrate Disc1 allele specific effects in the adult hippocampus, and suggest that the divergence in behavioural phenotypes may in part stem from changes in specific cell populations in the brain.
authors.affiliation: Medical Research Council Centre for Regenerative Medicine, Centre for Multiple Sclerosis Research, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Jayanth S
authors.initials: JS
authors.lastname: Chandran
authors.affiliation: Neurosciences, University of Cambridge, Department of Veterinary Medicine, Cambridge, United Kingdom.
authors.forename: Ilias
authors.initials: I
authors.lastname: Kazanis
authors.affiliation: Institute of Membrane and Systems Biology, University of Leeds, Leeds, United Kingdom.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Clapcote
authors.affiliation: Medical Genetics Section, Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Ogawa
authors.affiliation: Medical Genetics Section, Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: J Kirsty
authors.initials: JK
authors.lastname: Millar
authors.affiliation: Medical Genetics Section, Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: David J
authors.initials: DJ
authors.lastname: Porteous
authors.affiliation: Medical Research Council Centre for Regenerative Medicine, Centre for Multiple Sclerosis Research, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Charles
authors.initials: C
authors.lastname: Ffrench-Constant
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics; D004195:Disease Models, Animal; D015870:Gene Expression; D014644:Genetic Variation; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics*; D058953:Neural Stem Cells / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics*; D010641:Phenotype; D012559:Schizophrenia / Q000235:genetics
chemical_list: C498794:Disc1 protein, mouse; D009419:Nerve Tissue Proteins