Bontekoe, C.J.M.; Bakker, C.E.; Nieuwenhuizen, I.M.; van der Linde, H.; Lans, H.; de Lange, D; Hirst, M.C. and Oostra, B.A.
Instability of a (CGG)(98) repeat in the Fmr1 promoter.
Human Molecular Genetics, 10(16) pp. 1693–1699.
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.
||Some of the symbols may not have transferred correctly into this bibliographic record and/or abstract.
||Fragile-x-syndrome; uninterrupted CGG repeats; trinucleotide repeats; Huntingtons disease; triplet repeats; transgenic mice; cag repeat; secondary structure; hairpin structures; full mutation
||Science > Life, Health and Chemical Sciences
||02 Feb 2007
||02 Dec 2010 19:57
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