TY - JOUR
T1 - Disc1 variation leads to specific alterations in adult neurogenesis
AU - Chandran, Jayanth S.
AU - Kazanis, Ilias
AU - Clapcote, Steven J.
AU - Ogawa, Fumiaki
AU - Millar, J. Kirsty
AU - Porteous, David J.
AU - ffrench-Constant, Charles
N1 - Funding Information: CFFC is supported by a grant from the Wellcome Trust, which also provides strategic support (ISSF) for DP.
PY - 2014/10/1
Y1 - 2014/10/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84907495351&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0108088
DO - 10.1371/journal.pone.0108088
M3 - Article
C2 - 25272038
AN - SCOPUS:84907495351
VL - 9
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 10
M1 - 0108088
ER -