The contribution of GTF2I haploinsufficiency to Williams syndrome.
The contribution of GTF2I haploinsufficiency to Williams syndrome.
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DOI：
10.1016/j.mcp.2017.12.005
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发表时间：
2018-08
影响因子：
3.3
通讯作者：
Muotri AR
中科院分区：
文献类型：
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作者：
Chailangkarn T;Noree C;Muotri AR
威廉姆斯综合征 (WS) 是一种神经发育障碍，涉及多达 26-28 个基因的半缺失，导致一系列独特的身体、认知和行为表型。已使用多种模型（包括 WS 受试者、动物模型和外周细胞系）研究了每个基因的单倍体不足效应并与表型相关。然而，大多数基因与 WS 表型的联系仍不清楚。在这些基因中，通用转录因子 2I (GTF2I) 特别令人感兴趣，因为它的单倍体不足可能与 WS 的过度社交有关。在这里，我们描述了对非典型 WS 病例以及关注 GTF2I 的小鼠模型的研究，这些研究支持该蛋白在 WS 个体的神经认知和行为特征中的作用。我们还回顾了对 GTF2I 不同分子功能的集体研究，这些研究可能为我们最近报道的相关细胞模型（即 WS 诱导多能干细胞 (iPSC) 衍生神经元）的表型提供机制解释。最后，根据基因操作方法的进展，我们建议将其用于揭示 WS 背景下 GTF2I 的神经功能。
Williams syndrome (WS) is a neurodevelopmental disorder involving hemideletion of as many as 26–28 genes, resulting in a constellation of unique physical, cognitive and behavior phenotypes. The haploinsufficiency effect of each gene has been studied and correlated with phenotype(s) using several models including WS subjects, animal models, and peripheral cell lines. However, links for most of the genes to WS phenotypes remains unclear. Among those genes, general transcription factor 2I (GTF2I) is of particular interest as its haploinsufficiency is possibly associated with hypersociability in WS. Here, we describe studies of atypical WS cases as well as mouse models focusing on GTF2I that support a role for this protein in the neurocognitive and behavioral profiles of WS individuals. We also review collective studies on diverse molecular functions of GTF2I that may provide mechanistic explanation for phenotypes recently reported in our relevant cellular model, namely WS induced pluripotent stem cell (iPSC)-derived neurons. Finally, in light of the progress in gene-manipulating approaches, we suggest their uses in revealing the neural functions of GTF2I in the context of WS.