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Disc1 Variation Leads to Specific Alterations in Adult Neurogenesis

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 Di...

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Autores principales: Chandran, Jayanth S., Kazanis, Ilias, Clapcote, Steven J., Ogawa, Fumiaki, Millar, J. Kirsty, Porteous, David J., ffrench-Constant, Charles
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182707/
https://www.ncbi.nlm.nih.gov/pubmed/25272038
http://dx.doi.org/10.1371/journal.pone.0108088
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author Chandran, Jayanth S.
Kazanis, Ilias
Clapcote, Steven J.
Ogawa, Fumiaki
Millar, J. Kirsty
Porteous, David J.
ffrench-Constant, Charles
author_facet Chandran, Jayanth S.
Kazanis, Ilias
Clapcote, Steven J.
Ogawa, Fumiaki
Millar, J. Kirsty
Porteous, David J.
ffrench-Constant, Charles
author_sort Chandran, Jayanth S.
collection PubMed
description 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.
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spelling pubmed-41827072014-10-07 Disc1 Variation Leads to Specific Alterations in Adult Neurogenesis Chandran, Jayanth S. Kazanis, Ilias Clapcote, Steven J. Ogawa, Fumiaki Millar, J. Kirsty Porteous, David J. ffrench-Constant, Charles PLoS One Research Article 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. Public Library of Science 2014-10-01 /pmc/articles/PMC4182707/ /pubmed/25272038 http://dx.doi.org/10.1371/journal.pone.0108088 Text en © 2014 Chandran et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Chandran, Jayanth S.
Kazanis, Ilias
Clapcote, Steven J.
Ogawa, Fumiaki
Millar, J. Kirsty
Porteous, David J.
ffrench-Constant, Charles
Disc1 Variation Leads to Specific Alterations in Adult Neurogenesis
title Disc1 Variation Leads to Specific Alterations in Adult Neurogenesis
title_full Disc1 Variation Leads to Specific Alterations in Adult Neurogenesis
title_fullStr Disc1 Variation Leads to Specific Alterations in Adult Neurogenesis
title_full_unstemmed Disc1 Variation Leads to Specific Alterations in Adult Neurogenesis
title_short Disc1 Variation Leads to Specific Alterations in Adult Neurogenesis
title_sort disc1 variation leads to specific alterations in adult neurogenesis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182707/
https://www.ncbi.nlm.nih.gov/pubmed/25272038
http://dx.doi.org/10.1371/journal.pone.0108088
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