| 1 | 精神病学摩尔。2007年9月12: 833-41 |
|---|---|
| PMID | 17440435 |
| 标题 | The discoidin domain receptor 1 as a novel susceptibility gene for schizophrenia. |
| 抽象的 | Evidence suggests that myelin alterations could predispose toschizophrenia. Reduced expression of several myelin genes has been observed inschizophreniapatients. Recently, we identified the discoidin domain receptor 1 (DDR1; located at human chromosome 6p21.3) as a myelin gene in the mouse model and in a human oligodendroglial cell line. In the present study we screened for single nucleotide polymorphisms (SNPs) in the DNA from 100schizophreniapatients. We identified a novel mutation within exon 10 that produces the amino-acid substitution N502S in the a-d isoforms, and M475V in the e isoform. However the frequency of the mutation (2%) was similar inschizophrenia患者和对照对象。在389的病例对照评估中schizophrenicpatients and 615 controls, we identified one SNP (SNP9, rs1049623) associated withschizophrenia(odds ratio=1.44, 95% confidence interval: 1.15-1.79, adjusted P=0.0016). This association was confirmed in haplotype analysis; the SNPs 9-10-11 (rs1049623, rs2267641 and rs2239518) haplotype remaining significant even after adjustment for multiple testing (adjusted P=0.0136). Of note was a strong gender dependence in the association, that is, statistical significance restricted to men (adjusted P-value=0.0002). Regression analysis ofDDR1mRNA expression in peripheral blood lymphocytes fromschizophreniapatients showed that the presence of the G allele significantly decreased the relative number of mRNA copies in a dose-dependent manner (P=0.003). These data suggest that the risk haplotype tags a cis-acting variant involved in the transcription regulation system of the gene. In conclusion, we propose theDDR1as a new susceptibility gene forschizophrenia. |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 2 | 精神病学摩尔。2007年9月12: 833-41 |
| PMID | 17440435 |
| 标题 | The discoidin domain receptor 1 as a novel susceptibility gene for schizophrenia. |
| 抽象的 | Evidence suggests that myelin alterations could predispose toschizophrenia. Reduced expression of several myelin genes has been observed inschizophreniapatients. Recently, we identified the discoidin domain receptor 1 (DDR1; located at human chromosome 6p21.3) as a myelin gene in the mouse model and in a human oligodendroglial cell line. In the present study we screened for single nucleotide polymorphisms (SNPs) in the DNA from 100schizophreniapatients. We identified a novel mutation within exon 10 that produces the amino-acid substitution N502S in the a-d isoforms, and M475V in the e isoform. However the frequency of the mutation (2%) was similar inschizophrenia患者和对照对象。在389的病例对照评估中schizophrenicpatients and 615 controls, we identified one SNP (SNP9, rs1049623) associated withschizophrenia(odds ratio=1.44, 95% confidence interval: 1.15-1.79, adjusted P=0.0016). This association was confirmed in haplotype analysis; the SNPs 9-10-11 (rs1049623, rs2267641 and rs2239518) haplotype remaining significant even after adjustment for multiple testing (adjusted P=0.0136). Of note was a strong gender dependence in the association, that is, statistical significance restricted to men (adjusted P-value=0.0002). Regression analysis ofDDR1mRNA expression in peripheral blood lymphocytes fromschizophreniapatients showed that the presence of the G allele significantly decreased the relative number of mRNA copies in a dose-dependent manner (P=0.003). These data suggest that the risk haplotype tags a cis-acting variant involved in the transcription regulation system of the gene. In conclusion, we propose theDDR1as a new susceptibility gene forschizophrenia. |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 3 | J. Mol. Neurosci. 2009 May 38: 2-11 |
| PMID | 18836851 |
| 标题 | Discoidin domain receptor 1, a tyrosine kinase receptor, is upregulated in an experimental model of remyelination and during oligodendrocyte differentiation in vitro. |
| 抽象的 | 盘状蛋白结构域受体（DDR1）在神经发育过程中在少突胶质细胞中高度表达，并且在遗传上与schizophrenia. In this study, we aimed to further assess the involvement ofDDR1in both remyelination and oligodendrocyte differentiation. In the mouse model of demyelination-remyelination induced by oral administration of cuprizone, in situ hybridization showed an upregulation of theDDR1gene in three different white matter areas (corpus callosum, dorsal fornix, and external capsule) during the remyelination period. Moreover, real time reverse transcriptase polymerase chain reaction showed that the increase inDDR1Messenger RNA（mRNA）与数量密切相关DDR1-positive cells in the corpus callosum (Spearman coefficient = 0.987, P = 0.013). Cells positive forDDR1mRNA were also positive for oligodendrocyte markers (OLIG2, carnosine, and APC) but not for markers of oligodendrocyte precursors (NG2), myelin markers (CNPase), microglia (CD11b), or reactive glia (GFAP). Differentiation of a human oligodendroglial cell line, HOG16, was associated with an increase in mRNA expression ofDDR1and several myelin proteins (MBP and MOBP) but not other proteins (APC and CNPase). Here, we demonstrate thatDDR1is upregulated in vitro and in vivo when oligodendrocyte myelinating machinery is activated. Further studies are needed to identify the specific molecular pathway. |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 4 | 脑部。2010年6月1336日：22-9 |
| PMID | 20380825 |
| 标题 | Expression of the tyrosine kinase discoidin domain receptor 1 (DDR1) in human central nervous system myelin. |
| 抽象的 | During development of the mouse brain, the protein kinase discoidin domain receptor 1 (DDR1) is present prenatally in neurons of the proliferative areas, and postnatally,DDR1expression is no longer detected in neurons, but a spatial-temporal expression pattern in oligodendrocytes that overlaps with the dynamics of the myelination process is detected. Notably, oligodendrocyticDDR1expression is upregulated in mice during experimentally induced remyelination. Recently, we demonstrated thatDDR1expression is high in human brain and that there is an association between the gene andschizophreniain a case-control study. However, data regarding expression ofDDR1in the human brain are scarce. Here, we describe the expression pattern ofDDR1在人类的成年大脑皮层中。使用几种免疫组织学技术和原位杂交，我们确定了DDR1in the following: a) myelin, b) capillary endothelial cells in the gray as well as white matter, and c) in the soma of some oligodendrocytes and astrocytes in the white matter. The most important overall finding in this study was thatDDR1is present in myelin and is expressed by oligodendrocyte cells. We detected the presence ofDDR1mRNA and protein in myelin and observed thatDDR1与经典的髓磷脂碱性蛋白（MBP）共定位。此外，我们发现表达水平之间有很强的正相关DDR1and two myelin-associated genes, myelin-associated glycoprotein (MAG) and oligodendrocyte transcription factor 2 (OLIG2). These observations suggest thatDDR1could be an important constituent of myelin. Because defects in myelination are linked to several mental disorders such asschizophrenia, the function ofDDR1in the process of myelination warrants further investigation. |
| SCZ关键字 | 精神分裂症，精神分裂症 |