Properties of astrocytes cultured from GFAP over-expressing and GFAP mutant mice.
Properties of astrocytes cultured from GFAP over-expressing and GFAP mutant mice.
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DOI：
10.1016/j.yexcr.2008.12.012
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发表时间：
2009-04-15
影响因子：
3.7
通讯作者：
Messing A
中科院分区：
文献类型：
--
作者：
Cho W;Messing A
亚历山大病是一种致命的白质脑病，由 GFAP 的显性编码突变引起。先前的研究还表明 GFAP 绝对水平的升高是该疾病发病机制的核心。然而，目前尚不可能鉴定因 GFAP 错误表达而受损的关键星形胶质细胞功能。为了提供研究亚历山大病星形胶质细胞功能障碍性质的新工具，我们从两种亚历山大病小鼠模型中建立了原代星形胶质细胞培养物，一种过度表达野生型人类 GFAP 的转基因，以及模拟常见亚历山大病突变的内源性小鼠基因座的敲入。我们发现突变型 GFAP 以及过量的野生型 GFAP 会促进细胞质内含物的形成，破坏细胞骨架，减少细胞增殖，增加细胞死亡，降低蛋白酶体功能，并损害星形胶质细胞对应激的抵抗力。
Alexander disease is a fatal leukoencephalopathy caused by dominantly-acting coding mutations in GFAP. Previous work has also implicated elevations in absolute levels of GFAP as central to the pathogenesis of the disease. However, identification of the critical astrocyte functions that are compromised by mis-expression of GFAP has not yet been possible. To provide new tools for investigating the nature of astrocyte dysfunction in Alexander disease, we have established primary astrocyte cultures from two mouse models of Alexander disease, a transgenic that over-expresses wild type human GFAP, and a knock-in at the endogenous mouse locus that mimics a common Alexander disease mutation. We find that mutant GFAP, as well as excess wild type GFAP, promotes formation of cytoplasmic inclusions, disrupts the cytoskeleton, decreases cell proliferation, increases cell death, reduces proteasomal function, and compromises astrocyte resistance to stress.
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影响因子：
64.8
作者：
Kim, S;Wong, P;Coulombe, PA
通讯作者：
Coulombe, PA
影响因子：
7.5
作者：
Howe, A;Aplin, AE;Juliano, RL
通讯作者：
Juliano, RL
DOI：
10.1083/jcb.200602146
发表时间：
2006-07-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ku NO;Omary MB
通讯作者：
Omary MB
影响因子：
6.2
作者：
Acarin, Laia;Villapol, Sonia;Gonzalez, Berta
通讯作者：
Gonzalez, Berta
影响因子：
14.5
作者：
ALEXANDER, WS
通讯作者：
ALEXANDER, WS