Behavioral abnormalities and dopamine reductions in sdy mutant mice with a deletion in Dtnbp1, a susceptibility gene for schizophrenia.
Genetic susceptibility plays an important role in the pathogenesis of schizophrenia. Genetic evidence for an association between the dysbindin-1 gene (DTNBP1: dystrobrevin binding protein 1) and schizophrenia has been repeatedly reported in various populations worldwide. Thus, we performed behavioral analyses on homozygous sandy (sdy) mice, which lack dysbindin-1 owing to a deletion in the Dtnbp1 gene. Our results showed that sdy mice were less active and spent less time in the center of an open field apparatus. Consistent with the latter observation, sdy mice also displayed evidence of heightened anxiety-like response and deficits in social interaction. Compared to wild-type mice, sdy mice displayed lower levels of dopamine, but not glutamate, in the cerebral cortex, hippocampus, and hypothalamus. These findings indicate that sdy mice display a number of behavioral abnormalities associated with schizophrenia and suggest that these abnormalities may be mediated by reductions in forebrain dopamine transmission.
Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
Satoko
S
Hattori
Tomotaka
T
Murotani
Shinsuke
S
Matsuzaki
Tomoko
T
Ishizuka
Natsuko
N
Kumamoto
Masatoshi
M
Takeda
Masaya
M
Tohyama
Atsushi
A
Yamatodani
Hiroshi
H
Kunugi
Ryota
R
Hashimoto
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D004298:Dopamine / Q000378:metabolism*; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D020022:Genetic Predisposition to Disease; D018782:Maze Learning; D051379:Mice; D008817:Mice, Mutant Strains; D009043:Motor Activity; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D017384:Sequence Deletion; D012919:Social Behavior
D002352:Carrier Proteins; C498992:Dtnbp1 protein, mouse; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D004298:Dopamine