Bontekoe C J, Bakker C E, Nieuwenhuizen I M, van der Linde H, Lans H, de Lange D, Hirst M C, Oostra B A
CBG Department of Clinical Genetics, Erasmus University Rotterdam, PO Box 1738, 3000DR Rotterdam, The Netherlands.
Hum Mol Genet. 2001 Aug 1;10(16):1693-9. doi: 10.1093/hmg/10.16.1693.
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.
脆性X综合征是14种三核苷酸重复疾病之一。它是由于FMR1基因5'-非翻译区存在的CGG重复序列扩增而引起的，该序列的破坏会导致智力迟钝。三核苷酸重复序列扩增所涉及的机制尚不清楚，迄今为止，含有转基因扩增CGG重复序列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重复序列的基因组背景都被认为在扩增中起作用，我们现在已经构建了一种敲入小鼠Fmr1基因，其中小鼠的（CGG）8重复序列已被人类的（CGG）98重复序列所取代。与其他CGG转基因模型不同，该模型在母系和父系传递时均显示出适度的CGG重复序列不稳定性。该模型现在将使我们能够研究小鼠中重复序列扩增的时间和机制。
