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. and Ffrench-Constant, Charles ORCID: https://orcid.org/0000-0002-5621-3377 (2014) Disc1 variation leads to specific alterations in adult neurogenesis. PLoS One, 9 (10). ISSN 1932-6203

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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.

Item Type: Article
Additional Information: Funding Information: We thank Dr. Paul Kelly and Dr. J Kirsty Millar (University of Edinburgh) for maintaining the Disc1 mouse colony, the Medical Research Council (MRC) for funding JSC and NARSAD (Young Investigator Award to SJC) for funding the generation of the mutants. We thank K. Kaibuchi (Nagoya University) for kindly providing brain lysates from mice carrying a deletion of exons 2 and 3 of the Disc1 gene. We thank Ellen Grunewald and Helen Torrance for provision of materials and technical assistance. CFFC is supported by a grant from the Wellcome Trust, which also provides strategic support (ISSF) for DP.
Uncontrolled Keywords: biochemistry, genetics and molecular biology(all),agricultural and biological sciences(all),general ,/dk/atira/pure/subjectarea/asjc/1300
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 15 Jul 2022 22:30
Last Modified: 21 Jul 2022 11:39
URI: https://ueaeprints.uea.ac.uk/id/eprint/86259
DOI: 10.1371/journal.pone.0108088

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