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Weickert CS, Straub RE, McClintock BW, et al. Human Dysbindin (DTNBP1) Gene Expression inNormal Brain and in Schizophrenic Prefrontal Cortex and Midbrain. Arch Gen Psychiatry. 2004;61(6):544–555. doi:https://doi.org/10.1001/archpsyc.61.6.544
The schizophrenia-susceptibility gene dysbindin (DTNBP1 on 6p22.3) encodes a neuronal protein that binds to β-dystrobrevin
and may be part of the dystrophin protein complex. Little is known about dysbindin
expression in normal or schizophrenic brain.
To determine whether brain regions implicated in schizophrenia express
dysbindin and whether abnormal levels of dysbindin messenger RNA (mRNA) may
be found in this disorder and to test whether sequence variations in the dysbindin
gene in the promoter region, 5′ and 3′ untranslated regions, or
introns would affect dysbindin mRNA levels.
In patients with schizophrenia and controls, we compared dysbindin,
synaptophysin, spinophilin, and cyclophilin mRNA levels in the dorsolateral
prefrontal cortex and dysbindin mRNA levels in the midbrain by in situ hybridization.
We genotyped brain DNA at 11 single nucleotide polymorphisms to determine
whether genetic variation in the dysbindin gene affects cortical dysbindin
Main Outcome Measures
Quantitative assessment of dysbindin mRNA levels across various brain
regions and comparative studies of dysbindin mRNA levels in brains of patients
with schizophrenia compared with normal controls.
Dysbindin mRNA was detected in the frontal cortex, temporal cortex,
hippocampus, caudate, putamen, nucleus accumbens, amygdala, thalamus, and
midbrain of the adult brain. Patients with schizophrenia had statistically
significantly reduced dysbindin mRNA levels in multiple layers of the dorsolateral
prefrontal cortex, whereas synaptophysin, spinophilin, and cyclophilin mRNA
levels were unchanged. Dysbindin mRNA levels were quantitatively reduced in
the midbrain of patients with schizophrenia, but not statistically significantly.
Cortical dysbindin mRNA levels varied statistically significantly according
to dysbindin genotype.
Dysbindin mRNA is expressed widely in the brain, and its expression
is reduced in schizophrenia. Variation in dysbindin mRNA levels may be determined
in part by variation in the promoter and the 5′ and 3′ untranslated
regions. These data add to the evidence that dysbindin is an etiologic factor
in schizophrenia risk.
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