Instability of a (CGG)98 repeat in the Fmr1 promoter

被引：99

作者：

Bontekoe, CJM

Bakker, CE

Nieuwenhuizen, IM

van der Linde, H

Lans, H

de Lange, D

Hirst, MC

Oostra, BA

机构：

[1] Erasmus Univ, CBG Dept Clin Genet, NL-3000 DR Rotterdam, Netherlands

[2] Open Univ, Dept Biol Sci, Milton Keynes MK7 6AA, Bucks, England

来源：

HUMAN MOLECULAR GENETICS | 2001年 / 10卷 / 16期

关键词：

D O I：

10.1093/hmg/10.16.1693

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

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页码：1693 / 1699

页数：7

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