为此,研究者分离来自野生型和TDP-43Q331K敲入小鼠的小胶质细胞并在细胞中加入ODNs,实验表明TDP-43 Q331K 不影响ODNs诱导的TDP-43斑点形成,但是,当ODNs从细胞培养基中移除后,TDP-43胞质斑点的解离受到了阻碍,这一结果似乎并不是...
TDP-43 CTD 体外的研究发现，一些位于CR区域的点突变也能影响TDP-43 CTD的相分离，因此作者构建了A326P，M337P， Q331K，G294A，G335A等突变体，在细胞内研究这些突变体对于TDP43相分离的影响。当这些突变体在细胞内表达后，都能很好的定位到细胞核内，这些突变体通过相分离形成的“液滴”数量及通过FRAP测定...
研究人员选择了携带 ALS 相关 TDP-43 突变(Q331K)的敲入小鼠模型(TDP-43Q331K),通过基因敲除技术,让这些小鼠体内的 TMEM106B 基因失去功能,以此来观察相关变化。这项研究成果意义重大,它不仅揭示了 TMEM106B 和 TDP-43 在脂质代谢方面的新功能,还为深入理解神经退行性疾病的发病机制提供了新的视角,相关研究成果...
携带由 M323K Q331K Fratta等人(2018)产生的TDP‑43 或TDP‑43 的敲入小鼠还显示出功能剪接活性的增 加和神经肌肉和神经退行性表型。RNA识别基序2(RRM2)结构域中的F210I突变降低TDP‑43 的RNA/DNA结合能力并且在敲入小鼠中不引起任何运动表型。重要的是,F21 0I突变可以部 M323K F331I 分地挽救由化合物...
c Quantification of the experiments as in (a) showing the percentage of Hsp104DWB aggregates that enriched for TDP43Q331K or SOD1G93A. n = 45 cells examined over 3 independent experiments. The values of individual cells are plotted as dots, and the mean values of cells in the same...
a HEK293A cells transfected with vector, TDP-43-, TDP-43 Q331K-, and TDP-35-GFP plasmids were stained with transferrin-633 and endocytosis rate was determined by cellular incorporation (Supplementary Fig. 6a). Significance was assessed by one-way ANOVA. Repeated data are shown as mean ±...
Expression of human wild-type TDP-43 (TDP-43WT) caused no clinical or pathological phenotype, while expression of Q331K mutant (TDP-43Q331K) resulted in a non-lethal age-dependent motor phenotype, accompanied by cytoplasmic TDP-43 aggregation, mild neuronal loss, with astroglial and microglial...
mutation in its low complexity domain (TardbpQ331K) and suggested that skiptic splicing is a gain-of-function directly associated with disease-associated mutations [56]. Our data suggests that the observed increase in total TDP-43 in heterozygous and homozygous TardbpQ331Kmice likely mediates skip...
TDP-43WTxQ331Kmice demonstrate major neuronal loss, robust astroglial reactivity, increased cytoplasmic TDP-43 accumulation and detergent resistant TDP-43. We propose that mislocalisation and aggregation of the mutant protein seeds the rapid recruitment of wild-type TDP-43 that greatly accelerates the ...
The expression of TDP-43 mutations, including Q331K, M337V, Q343R, N345K, R361S, and N390D, has been shown to increase aggregation and cell toxicity in yeast cells41, and other disease-associated mutations, such as G294A, Q331K, M337V, Q343R, N390D, and N390S, enhance protein ...