Kif1Bβ isoform is enriched in motor neurons but does not change in a mouse model of amyotrophic lateral sclerosis
Kif1Bβ isoform is enriched in motor neurons but does not change in a mouse model of amyotrophic lateral sclerosis
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DOI：
10.1002/jnr.10517
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发表时间：
2003-03-01
影响因子：
4.2
通讯作者：
Bendotti, C
中科院分区：
文献类型：
--
作者：
Conforti, L;Dell'Agnello, C;Bendotti, C
驱动蛋白超家族马达蛋白Kif 1B以两种同种型Kif 1B α和Kif 1B β表达，具有不同的货物结合结构域。我们研究了mRNA的两种异构体在相邻的部分成年小鼠的脑和脊髓原位杂交分析。Kif 1B β mRNA在脑和脊髓的几个区域富集。它的水平比几乎检测不到的α亚型高出四到五倍。Kif 1B β的mRNA水平最高的大脑皮层，海马，小脑和脊髓灰质。在细胞水平上，延髓运动核团和脊髓前角运动神经元信号最强。由于其他Kif基因的表达在肌萎缩侧索硬化（ALS）模型中改变，我们研究了携带SOD 1G 93 A突变的转基因小鼠（家族性ALS模型）在症状前和疾病早期脊髓中Kif 1B β mRNA的表达水平。在运动神经元或脊髓其他区域中未观察到Kif 1B β mRNA的变化。这些发现表明，Kif 1B α，调节线粒体的运输，可能在中枢神经系统以外的组织中发挥重要作用。相反，Kif 1B β，负责突触囊泡前体的运输，似乎在神经系统中发挥重要作用，特别是在下运动神经元中。在转基因SOD 1G 93 A小鼠中Kif 1B β mRNA的变化的情况下，表明其他分子机制可能在这些小鼠的运动神经元中发生的轴突运输的破坏中发挥作用。(C)2002 Wiley-Liss，Inc.
The kinesin superfamily motor protein Kif1B is expressed in two isoforms, Kif1Balpha and Kif1Bbeta, with distinct cargo-binding domains. We examined the mRNA distribution of the two isoforms in adjacent sections of brain and spinal cord of adult mice using in situ hybridization analysis. Kif1Bbeta mRNA is enriched in several regions of brain and spinal cord. Its levels are four to five times higher than that of the alpha isoform, which was barely detectable. The highest mRNA levels of Kif1Bbeta were found in the cortex, hippocampus, cerebellum and the grey matter of the spinal cord. At the cellular level the highest signal was found in motor neurons in the motor nuclei of medulla oblongata and the ventral horn of spinal cord. Because expression of other Kif genes is altered in amyotrophic lateral sclerosis (ALS) models, we examined the expression level of Kif1Bbeta mRNA in the spinal cord of transgenic mice carrying the SOD1G93A mutation, a model of familial ALS, at presymptomatic and early stages of the disease. No changes were observed in Kif1Bbeta mRNA in motor neurons or in other regions of the spinal cord. These findings indicate that Kif1Balpha, which modulates the transport of mitochondria, may play a major role in tissues other than the central nervous system. Instead Kif1Bbeta, responsible for the transport of synaptic vesicle precursors, seems to play an important role in the nervous system, particularly in the lower motor neurons. The absence of changes of Kif1Bbeta mRNA in transgenic SOD1G93A mice suggests that other molecular mechanisms may play a role in the disruption of axonal transport occurring in the motor neurons of these mice. (C) 2002 Wiley-Liss, Inc.