Instability of a (CGG)98 repeat in the Fmr1 promoter
Instability of a (CGG)98 repeat in the Fmr1 promoter
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DOI：
10.1093/hmg/10.16.1693
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发表时间：
2001-08-01
影响因子：
3.5
通讯作者：
Oostra, BA
中科院分区：
文献类型：
--
作者：
Bontekoe, CJM;Bakker, CE;Oostra, BA
脆性X综合征是14种三核苷酸重复疾病之一。它是由于存在于 FMR1 基因 5'-非翻译区的 CGG 重复序列的扩展而产生的，其破坏会导致智力低下。人们对三核苷酸重复扩增所涉及的机制知之甚少，迄今为止，含有转基因扩增CGG重复的转基因小鼠模型未能重现人类中所见的不稳定性。由于顺式作用因子和 CGG 重复序列的基因组环境都被认为在扩增中发挥作用，因此我们现在生成了敲入小鼠 Fmr1 基因，其中鼠 (CGG)(8) 重复序列已与人 (CGG)(98) 重复序列交换。与其他 CGG 转基因模型不同，该模型在母本和父本传播中均表现出中等程度的 CGG 重复不稳定性。该模型现在将使我们能够研究小鼠重复扩增的时间和机制。
Fragile X syndrome is one of 14 trinucleotide repeat diseases. It arises due to expansion of a CGG repeat which is present in the 5 ' -untranslated region of the FMR1 gene, disruption of which leads to mental retardation. The mechanisms involved in trinucleotide repeat expansion are poorly understood and to date, transgenic mouse models containing transgenic expanded CGG repeats have failed to reproduce the instability seen in humans. As both cis-acting factors and the genomic context of the CGG repeat are thought to play a role in expansion, we have now generated a knock-in mouse Fmr1 gene in which the murine (CGG)(8) repeat has been exchanged with a human (CGG)(98) repeat. Unlike other CGG transgenic models, this model shows moderate CGG repeat instability upon both in maternal and paternal transmission. This model will now enable us to study the timing and the mechanism of repeat expansion in mice.