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首页> 外文期刊>The European Journal of Neuroscience >Age-dependent increase in Kalirin-9 and Kalirin-12 transcripts in human orbitofrontal cortex
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Age-dependent increase in Kalirin-9 and Kalirin-12 transcripts in human orbitofrontal cortex

机译:人眶额皮质中Kalirin-9和Kalirin-12转录本的年龄依赖性增加

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KALRN (KAL) is a Rho GEF that is highly involved in regulation of the actin cytoskeleton within dendrites. There are several isoforms of the protein that arise from differential splicing of KALRN's 66 exons. KAL isoforms have different functions in development. For example, overexpression of the KAL9 and KAL12 isoforms induce dendritic elongation in early development. However, in mature neurons KAL9 overexpression reduces dendritic length, a phenotype also observed in normal human ageing. We therefore hypothesized that KAL9 would have increased expression with age, and undertook to evaluate the expression of individual KALRN exons throughout the adult lifespan. Postmortem human brain grey matter from Brodmann's area (BA) 11 and BA47 derived from a cohort of 209 individuals without psychiatric or neurodegenerative disease, ranging in age from 16 to 91 years, were analysed for KALRN expression by Affymetrix exon array. Analysis of the exon array data in an isoform-specific manner, as well as confirmatory isoform-specific qPCR studies, indicated that the longer KAL9 and KAL12 isoforms demonstrated a statistically significant, but modest, increase with age. The small magnitude of the age effect suggests that inter-individual factors other than age likely contribute to a higher degree to KAL9 and KAL12 expression. In contrast to KAL9 and KAL12, global KALRN expression did not increase with age. Our work suggests that global measures of KALRN gene expression may be misleading and future studies should focus on isoform-specific quantification.
机译:KALRN(KAL)是Rho GEF,它高度参与树突中肌动蛋白细胞骨架的调节。 KALRN的66个外显子的差异剪接产生了蛋白质的几种同工型。 KAL同工型在开发中具有不同的功能。例如,KAL9和KAL12亚型的过表达会在早期发育中诱导树突伸长。但是,在成熟的神经元中,KAL9的过度表达会降低树突长度,这也是在正常人的年龄中也观察到的一种表型。因此,我们假设KAL9的表达会随着年龄的增长而增加,并承诺评估整个成人寿命中单个KALRN外显子的表达。使用Affymetrix外显子阵列分析了来自Brodmann病区(BA)11和BA47的死后人脑灰质,其来自209名无精神病或神经退行性疾病的人群,年龄在16至91岁之间。以同工型特异性方式对外显子阵列数据进行分析,以及证实性同工型特异性qPCR研究表明,较长的KAL9和KAL12同工型随着年龄的增长具有统计学意义,但适度增加。年龄效应的幅度较小表明,年龄以外的个体因素可能对KAL9和KAL12的表达有较高的影响。与KAL9和KAL12相反,整体KALRN表达并未随年龄增长。我们的工作表明,对KALRN基因表达的整体测量可能会产生误导,未来的研究应侧重于异构体特异性定量。

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