Human Molecular Genetics, Vol 7, 1285-1291, Copyright © 1998 by Oxford University Press
AS Lia, H Seznec, H Hofmann-Radvanyi, F Radvanyi, C Duros, C Saquet, M Blanche, C Junien and G Gourdon
A (CTG)nexpansion in the 3'-untranslated region (UTR) of the DM protein
kinase gene ( DMPK ) is responsible for causing myotonic dystrophy (DM).
Major instability, with very large expansions between generations and high
levels of somatic mosaicism, is observed in patients. There is a good
correlation between repeat size (at least in leucocytes), clinical severity
and age of onset. The trinucleotide repeat instability mechanisms involved
in DM and other human genetic diseases are unknown. We studied somatic
instability by measuring the CTG repeat length at several ages in various
tissues of transgenic mice carrying a (CTG)55expansion surrounded by 45 kb
of the human DM region, using small-pool PCR. These mice have been shown to
reproduce the intergenerational and somatic instability of the 55 CTG
repeat suggesting that surrounding sequences and the chromatin environment
are involved in instability mechanisms. As observed in some of the tissues
of DM patients, there is a tendency for repeat length and somatic mosaicism
to increase with the age of the mouse. Furthermore, we observed no
correlation between the somatic mutation rate and tissue proliferation
capacity. The somatic mutation rates in different tissues were also not
correlated to the relative inter-tissue difference in transcriptional
levels of the three genes (DMAHP , DMPK and 59) surrounding the repeat.
ARTICLES
Somatic instability of the CTG repeat in mice transgenic for the myotonic dystrophy region is age dependent but not correlated to the relative intertissue transcription levels and proliferative capacities
INSERM UR383, Hopital Necker-Enfants Malades, clinique Maurice Lamy, 149-161 rue de Sevres, 75743 Paris, Cedex 15, France.
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