A mouse model for the basal transcription DNA repair syndrome trichothiodystrophy
A mouse model for the basal transcription DNA repair syndrome trichothiodystrophy
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DOI：
10.1016/s1097-2765(00)80098-2
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发表时间：
1998-06-01
期刊：
影响因子：
16
通讯作者：
Weeda, G
中科院分区：
文献类型：
--
作者：
de Boer, J;de Wit, J;Weeda, G
日光敏感型严重神经发育、脆性毛发紊乱(TTD)是由双功能DNA修复/基础转录因子TFIIH的基本XPB和XPD解旋酶亚基的点突变引起的。表型被假设部分来自核苷酸切除修复缺陷，部分来自微妙的碱基转录缺陷，解释了不可修复的TTD特征。使用一种新的基因靶向策略，我们在小鼠身上模拟了一名TTD患者的致病XPD点突变。TTD小鼠在很大程度上反映了人类的疾病，包括毛发脆弱、发育异常、寿命缩短、对紫外线的敏感性和皮肤异常。皮肤症状与一种皮肤特异性基因转录减少有关，这有力地支持了TTD是一种人类疾病的概念，这是由于基础转录和DNA修复方面的先天缺陷。
The sun-sensitive form of the severe neurodevelopmental, brittle hair disorder trichothiodystrophy (TTD) is caused by point mutations in the essential XPB and XPD helicase subunits of the dual functional DNA repair/basal transcription factor TFIIH. The phenotype is hypothesized to be in part derived from a nucleotide excision repair defect and in part from a subtle basal transcription deficiency accounting for the nonrepair TTD features. Using a novel gene-targeting strategy, we have mimicked the causative XPD point mutation of a TTD patient in the mouse. TTD mice reflect to a remarkable extent the human disorder, including brittle hair, developmental abnormalities, reduced life span, UV sensitivity, and skin abnormalities. The cutaneous symptoms are associated with reduced transcription of a skin-specific gene, strongly supporting the concept of TTD as a human disease due to inborn defects in basal transcription and DNA repair.