Expression of kinase interacting with stathmin (KIS, UHMK1) in human brain and lymphoblasts: Effects of schizophrenia and genotype.
Expression of kinase interacting with stathmin (KIS, UHMK1) in human brain and lymphoblasts: Effects of schizophrenia and genotype.
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DOI：
10.1016/j.brainres.2009.08.090
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发表时间：
2009-12-08
期刊：
影响因子：
2.9
通讯作者：
Eastwood, Sharon L.
中科院分区：
文献类型：
--
作者：
Bristow, Greg C.;Lane, Tracy A.;Walker, Mary;Chen, Li;Sei, Yoshi;Hyde, Thomas M.;Kleinman, Joel E.;Harrison, Paul J.;Eastwood, Sharon L.
编码丝氨酸/苏氨酸激酶KIS（与Stathmin相互作用的激酶，也称为UHMK 1）的基因内的单核苷酸多态性（SNP）最近与精神分裂症相关。由于与疾病相关的SNPs都不编码，它们可能通过改变KIS表达的某些方面而赋予易感性。在这里，我们的特点是细胞分布KIS在人脑中使用原位杂交和免疫组化，并定量KIS蛋白和mRNA在两个大的大脑系列，以确定KIS表达是否改变精神分裂症或双相情感障碍或精神分裂症相关的SNP（rs7513662）。尸检组织的上级颞回的精神分裂症和对照组，也背外侧前额叶皮层，前扣带皮层，小脑的精神分裂症，双相情感障碍，和对照组。KIS的表达测定定量PCR（mRNA）和免疫放射自显影（蛋白质），并在淋巴母细胞系来自精神分裂症和对照组的免疫印迹定量。我们的研究结果表明，KIS在神经元中表达，其编码的蛋白质定位于细胞核和细胞质。在诊断组之间或在淋巴母细胞系中没有发现KIS表达的差异，并且没有发现rs7513662基因型对KIS表达的影响。因此，这些数据没有提供支持表达改变是KIS遗传变异可能增加精神分裂症易感性的机制的假设，也没有证据表明KIS表达在疾病本身中改变，至少在这里研究的参数方面。
Single nucleotide polymorphisms (SNPs) within the gene encoding the serine/threonine kinase KIS (Kinase Interacting with Stathmin, also known as UHMK1) have recently been associated with schizophrenia. As none of the disease associated SNPs are coding, they may confer susceptibility by altering some facet of KIS expression. Here we have characterised the cellular distribution of KIS in human brain using in situ hybridisation and immunohistochemistry, and quantified KIS protein and mRNA in two large brain series to determine if KIS expression is altered in schizophrenia or bipolar disorder or in relation to a schizophrenia-associated SNP (rs7513662). Post-mortem tissue from the superior temporal gyrus of schizophrenia and control subjects, and also dorsolateral prefrontal cortex, anterior cingulate cortex, and cerebellum from schizophrenia, bipolar disorder, and control subjects were used. KIS expression was measured by quantitative PCR (mRNA) and immunoautoradiography (protein), and was also quantified by immunoblot in lymphoblast cell lines derived from schizophrenia and control subjects. Our results demonstrate that KIS is expressed in neurons, and its encoded protein is localised to the nucleus and cytoplasm. No difference in KIS expression was found between diagnostic groups, or in the lymphoblast cell lines, and no effect of rs7513662 genotype on KIS expression was found. Hence, these data do not provide support for the hypothesis that altered expression is the mechanism by which genetic variation of KIS may increase susceptibility to schizophrenia, nor evidence that KIS expression is altered in the disease itself, at least in terms of the parameters studied here.
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影响因子：
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