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肌萎缩侧索硬化转基因小鼠模型中tau异构体的表达

Tau isoforms expression in transgenic mouse model of amyotrophic lateral sclerosis.

作者信息

Usarek Ewa, Kuźma-Kozakiewicz Magdalena, Schwalenstöcker Birgit, Kaźmierczak Beata, Münch Christoph, Ludolph Albert C, Barańczyk-Kuźma Anna

机构信息

Department of Biochemistry, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland.

出版信息

Neurochem Res. 2006 May;31(5):597-602. doi: 10.1007/s11064-006-9057-3. Epub 2006 May 23.

DOI:10.1007/s11064-006-9057-3
PMID:16770730
Abstract

Tau is a protein involved in regulation of microtubule stability, axonal differentiation and transport. Alteration of retrograde transport may lead to motor neuron degeneration. Thus alternative mRNA splicing and expression of tau isoforms were studied in a transgenic mouse model harboring the human SOD1 G93A mutation. The studies were performed on cortex, hippocampus and spinal cord of 64- and 120-day-old animals (presymptomatic and symptomatic stage) and wild type controls. Exon 10 was found in all studied tissues. The 2N isoform containing exons 2 and 3 (+2+3) and the 1N (+2-3) predominated over the 0N (-2-3) in brain regions of the studied mice. The 2N expression was significantly lower in cortex and hippocampus of symptomatic animals compared to analogue control tissues. The decrease in 2N expression resulted in lower levels of total tau mRNA and tau protein. No changes in tau expression were observed in spinal cord of studied animals.

摘要

Tau是一种参与微管稳定性调节、轴突分化和运输的蛋白质。逆行运输的改变可能导致运动神经元变性。因此,在携带人SOD1 G93A突变的转基因小鼠模型中研究了tau异构体的可变mRNA剪接和表达。对64日龄和120日龄动物(症状前期和症状期)以及野生型对照的皮质、海马体和脊髓进行了研究。在所研究的所有组织中均发现了外显子10。在所研究小鼠的脑区中,包含外显子2和3(+2+3)的2N异构体和1N(+2-3)异构体比0N(-2-3)异构体占优势。与对照组织相比,症状期动物的皮质和海马体中2N的表达显著降低。2N表达的降低导致总tau mRNA和tau蛋白水平降低。在所研究动物的脊髓中未观察到tau表达的变化。

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Mice with mutation in dynein heavy chain 1 do not share the same tau expression pattern with mice with SOD1-related motor neuron disease.携带动力蛋白重链 1 突变的小鼠与 SOD1 相关运动神经元疾病的小鼠表现出不同的 tau 表达模式。
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