Abstract:
BACKGROUND:Solid evidence links schizophrenia (SZ) susceptibility to neurodevelopmental processes involving tyrosine phosphorylation-mediated signaling. Mouse studies implicate the Ptpra gene, encoding protein tyrosine phosphatase RPTPα, in the control of radial neuronal migration, cortical cytoarchitecture, and oligodendrocyte differentiation. The human gene encoding RPTPα, PTPRA, maps to a chromosomal region (20p13) associated with susceptibility to psychotic illness. METHODS:We characterized neurobehavioral parameters, as well as gene expression in the central nervous system, of mice with a null mutation in the Ptpra gene. We searched for genetic association between polymorphisms in PTPRA and schizophrenia risk (two independent cohorts, 1420 cases and 1377 controls), and we monitored PTPRA expression in prefrontal dorsolateral cortex of SZ patients (35 cases, 2 control groups of 35 cases). RESULTS:We found that Ptpra⁻/⁻ mice reproduce neurobehavioral endophenotypes of human SZ: sensitization to methamphetamine-induced hyperactivity, defective sensorimotor gating, and defective habituation to a startle response. Ptpra loss of function also leads to reduced expression of multiple myelination genes, mimicking the hypomyelination-associated changes in gene expression observed in postmortem patient brains. We further report that a polymorphism at the PTPRA locus is genetically associated with SZ, and that PTPRA mRNA levels are reduced in postmortem dorsolateral prefrontal cortex of subjects with SZ. CONCLUSIONS:The implication of this well-studied signaling protein in SZ risk and endophenotype manifestation provides novel entry points into the etiopathology of this disease.
journal_name
Biol Psychiatryjournal_title
Biological psychiatryauthors
Takahashi N,Nielsen KS,Aleksic B,Petersen S,Ikeda M,Kushima I,Vacaresse N,Ujike H,Iwata N,Dubreuil V,Mirza N,Sakurai T,Ozaki N,Buxbaum JD,Sap Jdoi
10.1016/j.biopsych.2011.06.016subject
Has Abstractpub_date
2011-10-01 00:00:00pages
626-35issue
7eissn
0006-3223issn
1873-2402pii
S0006-3223(11)00637-8journal_volume
70pub_type
杂志文章abstract:BACKGROUND:Antenatal maternal cortisol levels associate with alterations in the amygdala, a structure associated with emotion regulation, in the offspring. However, because offspring brain and behavior are commonly assessed years after birth, the timing of such maternal influences is unclear. This study aimed to examin...
journal_title:Biological psychiatry
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journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Biological psychiatry
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更新日期:1988-01-15 00:00:00
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更新日期:2005-07-15 00:00:00
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更新日期:2012-11-15 00:00:00
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pub_type: 杂志文章,随机对照试验
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journal_title:Biological psychiatry
pub_type: 杂志文章
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更新日期:2009-06-15 00:00:00
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journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章
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更新日期:1994-07-15 00:00:00
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pub_type: 杂志文章
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更新日期:2012-11-15 00:00:00
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pub_type: 杂志文章
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更新日期:2001-09-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
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更新日期:2015-11-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:
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