The human homolog of the QKI gene affected in the severe dysmyelination "quaking" mouse phenotype: downregulated in multiple brain regions in schizophrenia.
OBJECTIVE
The authors sought to understand the origins of oligodendrocyte/myelin gene expression abnormalities in the brains of persons with schizophrenia.


METHODS
Twelve cortical regions (Brodmann's areas 8, 10, 44, 46, 23/31, 24/32, 20, 21, 22, 36/28, 7, and 17) and three noncortical regions (caudate, hippocampus, and putamen) of 16 elderly schizophrenia patients and 14 matched comparison subjects were examined using 450 separate microarrays. The mRNA levels of QKI and its isoforms were then measured in a larger cohort by using quantitative real-time polymerase chain reaction (qPCR) in the cingulate cortex of schizophrenia subjects and matched comparison subjects.


RESULTS
Expression of QKI mRNA was decreased in seven cortical regions and the hippocampus in the schizophrenia subjects. QKI gene expression deficits detected by microarray were validated by qPCR in the cingulate cortex, where the expression of isoforms QKI-5, QKI-6, and QKI-7 were profoundly perturbed in schizophrenia.


CONCLUSIONS
Since QKI plays a fundamental role in oligodendrocyte differentiation and in myelination, its underexpression may be pivotal to, and upstream of, other myelin-associated gene expression abnormalities in schizophrenia. Given the role of QKI in determination of oligodendrocyte fate, these results not only confirm oligodendrocyte-related gene expression abnormalities in schizophrenia but suggest that the physiology of glial progenitor cells may be altered in schizophrenia.
Haroutunian
Vahram
V
Department of Psychiatry, Rm. 4F-33A, Bronx VA Medical Center, 130 W. Kingsbridge Rd., Bronx, NY 10468, USA. vahram.haroutunian@mssm.edu
Katsel
Pavel
P
Dracheva
Stella
S
Davis
Kenneth L
KL
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D003711:Demyelinating Diseases / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008821:Mice, Quaking; D009185:Myelin Proteins / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics*; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*
D009185:Myelin Proteins; D020033:Protein Isoforms; C490832:QKI protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins