Detergent-insoluble inclusion constitutes the first pathology in PFN1 transgenic rats.
Detergent-insoluble inclusion constitutes the first pathology in PFN1 transgenic rats.
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DOI：
10.1111/jnc.15139
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发表时间：
2021-05
影响因子：
4.7
通讯作者：
Xia XG
中科院分区：
文献类型：
--
作者：
Yuan G;Cui S;Chen X;Song H;Huang C;Tong J;Yuan Z;Yu L;Xiong X;Zhao J;Huang B;Wu Q;Zhou Y;Chen G;Zhou H;Xia XG
Profilin 1（PFN1）突变可导致肌萎缩侧索硬化症（ALS）。为了评估PFN1突变如何引发该疾病，我们利用含有人PFN1基因编码序列和调控序列的人类基因组DNA培育了转基因大鼠。所选的转基因品系以适中且相当的水平，并以与大鼠内源性PFN1相似的时空表达模式表达含或不含致病突变C71G的人PFN1。在cDNA转基因动物中常见的任意转基因表达的人为影响在PFN1转基因大鼠中被降至最低。在大鼠中表达突变型（而非野生型）人PFN1重现了ALS的主要特征，包括运动神经元进行性丧失以及随后的骨骼肌失神经萎缩。在表达突变型人PFN1但无症状的转基因大鼠中，首先检测到耐洗涤剂的PFN1包涵体这种病理现象。这些发现表明，蛋白质聚集参与了与PFN1突变相关的ALS神经退行性变。由此产生的大鼠模型对ALS的机制研究是有用的。
Mutation of profilin 1 (PFN1) can cause amyotrophic lateral sclerosis (ALS). To assess how PFN1 mutation causes the disease, we created transgenic rats with human genomic DNA that harbors both the coding and the regulatory sequences of the human PFN1 gene. Selected transgenic lines expressed human PFN1 with or without the pathogenic mutation C71G at a moderate and a comparable level and in the similar pattern of spatial and temporal expression to rat endogenous PFN1. The artificial effects of arbitrary transgene expression commonly observed in cDNA transgenic animals were minimized in PFN1 transgenic rats. Expression of the mutant, but not the wild type, human PFN1 in rats recapitulated the cardinal features of ALS including the progressive loss of motor neurons and the subsequent denervation atrophy of skeletal muscles. Detergent-insoluble PFN1 inclusions were detected as the first pathology in otherwise asymptomatic transgenic rats expressing mutant human PFN1. The findings suggest that protein aggregation is involved in the neurodegeneration of ALS associated with PFN1 mutation. The resulting rat model is useful to mechanistic study on the ALS.
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影响因子：
8
作者：
通讯作者：
--
影响因子：
4.2
作者：
Smith BN;Vance C;Scotter EL;Troakes C;Wong CH;Topp S;Maekawa S;King A;Mitchell JC;Lund K;Al-Chalabi A;Ticozzi N;Silani V;Sapp P;Brown RH Jr;Landers JE;Al-Sarraj S;Shaw CE
通讯作者：
Shaw CE
影响因子：
3.5
作者：
Fil D;DeLoach A;Yadav S;Alkam D;MacNicol M;Singh A;Compadre CM;Goellner JJ;O'Brien CA;Fahmi T;Basnakian AG;Calingasan NY;Klessner JL;Beal FM;Peters OM;Metterville J;Brown RH Jr;Ling KKY;Rigo F;Ozdinler PH;Kiaei M
通讯作者：
Kiaei M
DOI：
10.1002/mds.27296
发表时间：
2018-05
期刊：
Movement disorders : official journal of the Movement Disorder Society
影响因子：
--
作者：
Creed RB;Goldberg MS
通讯作者：
Goldberg MS
影响因子：
2.9
作者：
Rennella, Enrico;Sekhar, Ashok;Kay, Lewis E.
通讯作者：
Kay, Lewis E.