Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (50)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Seznec, H.
Right arrow Articles by Gourdon, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Seznec, H.
Right arrow Articles by Gourdon, G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, 2000, Vol. 9, No. 8 1185-1194
© 2000 Oxford University Press

Transgenic mice carrying large human genomic sequences with expanded CTG repeat mimic closely the DM CTG repeat intergenerational and somatic instability

Hervé Seznec, Anne-Sophie Lia-Baldini1, Chantal Duros, Coralie Fouquet, Céline Lacroix, Hélène Hofmann-Radvanyi2, Claudine Junien and Geneviève Gourdon+

INSERM UR383, Hôpital Necker-Enfants Malades, Université René Descartes Paris V, Paris, France, 1Division of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA and 2Laboratoire de Biochimie, Hôpital Ambroise Paré, Boulogne, France

Myotonic dystrophy (DM) is caused by a CTG repeat expansion in the 3'UTR of the DM protein kinase (DMPK) gene. A very high level of instability is observed through successive generations and the size of the repeat is generally correlated with the severity of the disease and with age at onset. Furthermore, tissues from DM patients exhibit somatic mosaicism that increases with age. We generated transgenic mice carrying large human genomic sequences with 20, 55 or >300 CTG, cloned from patients from the same affected DM family. Using large human flanking sequences and a large amplification, we demonstrate that the intergenerational CTG repeat instability is reproduced in mice, with a strong bias towards expansions and with the same sex- and size-dependent characteristics as in humans. Moreover, a high level of instability, increasing with age, can be observed in tissues and in sperm. Although we did not observe dramatic expansions (or ‘big jumps’ over several hundred CTG repeats) as in congenital forms of DM, our model carrying >300 CTG is the first to show instability so close to the human DM situation. Our three models carrying different sizes of CTG repeat provide insight on the different factors modulating the CTG repeat instability.

+ To whom correspondence should be addressed. Tel: +33 1 44 49 45 23; Fax: +33 1 47 83 32 06; Email: gourdon@necker.fr


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
S. A. M. Mulders, W. J. A. A. van den Broek, T. M. Wheeler, H. J. E. Croes, P. van Kuik-Romeijn, S. J. de Kimpe, D. Furling, G. J. Platenburg, G. Gourdon, C. A. Thornton, et al.
Triplet-repeat oligonucleotide-mediated reversal of RNA toxicity in myotonic dystrophy
PNAS, August 18, 2009; 106(33): 13915 - 13920.
[Abstract] [Full Text] [PDF]

Home page
 Microbiol. Mol. Biol. Rev.Home page
G.-F. Richard, A. Kerrest, and B. Dujon
Comparative Genomics and Molecular Dynamics of DNA Repeats in Eukaryotes
Microbiol. Mol. Biol. Rev., December 1, 2008; 72(4): 686 - 727.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
R. Zahra, J. K. Blackwood, J. Sales, and D. R. F. Leach
Proofreading and Secondary Structure Processing Determine the Orientation Dependence of CAG{middle dot}CTG Trinucleotide Repeat Instability in Escherichia coli
Genetics, May 1, 2007; 176(1): 27 - 41.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
I.V. Kovtun, A.R. Thornhill, and C.T. McMurray
Somatic deletion events occur during early embryonic development and modify the extent of CAG expansion in subsequent generations
Hum. Mol. Genet., December 15, 2004; 13(24): 3057 - 3068.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
V. I. Hashem, M. J. Pytlos, E. A. Klysik, K. Tsuji, M. Khajav, T. Ashizawa, and R. R. Sinden
Chemotherapeutic deletion of CTG repeats in lymphoblast cells from DM1 patients
Nucleic Acids Res., December 1, 2004; 32(21): 6334 - 6346.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
M. Gomes-Pereira, M. T. Fortune, L. Ingram, J. P. McAbney, and D. G. Monckton
Pms2 is a genetic enhancer of trinucleotide CAG{middle dot}CTG repeat somatic mosaicism: implications for the mechanism of triplet repeat expansion
Hum. Mol. Genet., August 15, 2004; 13(16): 1815 - 1825.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
C. Savouret, C. Garcia-Cordier, J. Megret, H. te Riele, C. Junien, and G. Gourdon
MSH2-Dependent Germinal CTG Repeat Expansions Are Produced Continuously in Spermatogonia from DM1 Transgenic Mice
Mol. Cell. Biol., January 15, 2004; 24(2): 629 - 637.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
R. Willemsen, M. Hoogeveen-Westerveld, S. Reis, J. Holstege, L.-A. W.F.M. Severijnen, I. M. Nieuwenhuizen, M. Schrier, L. van Unen, F. Tassone, A. T. Hoogeveen, et al.
The FMR1 CGG repeat mouse displays ubiquitin-positive intranuclear neuronal inclusions; implications for the cerebellar tremor/ataxia syndrome
Hum. Mol. Genet., May 1, 2003; 12(9): 949 - 959.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
T. Nenguke, M. I. Aladjem, J. F. Gusella, N. S. Wexler, The Venezuela HD Project, and N. Arnheim
Candidate DNA replication initiation regions at human trinucleotide repeat disease loci
Hum. Mol. Genet., May 1, 2003; 12(9): 1021 - 1028.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
R. T. Libby, D. G. Monckton, Y.-H. Fu, R. A. Martinez, J. P. McAbney, R. Lau, D. D. Einum, K. Nichol, C. B. Ware, L. J. Ptacek, et al.
Genomic context drives SCA7 CAG repeat instability, while expressed SCA7 cDNAs are intergenerationally and somatically stable in transgenic mice
Hum. Mol. Genet., January 1, 2003; 12(1): 41 - 50.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
S. Bhattacharyya, M. L. Rolfsmeier, M. J. Dixon, K. Wagoner, and R. S. Lahue
Identification of RTG2 as a Modifier Gene for CTG{middle dot}CAG Repeat Instability in Saccharomyces cerevisiae
Genetics, October 1, 2002; 162(2): 579 - 589.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
Y. Zhang, D. G. Monckton, M. J. Siciliano, T. H. Connor, and M. L. Meistrich
Age and insertion site dependence of repeat number instability of a human DM1 transgene in individual mouse sperm
Hum. Mol. Genet., April 1, 2002; 11(7): 791 - 798.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
W. J. A. A. van den Broek, M. R. Nelen, D. G. Wansink, M. M. Coerwinkel, H. te Riele, P. J. T. A. Groenen, and B. Wieringa
Somatic expansion behaviour of the (CTG)n repeat in myotonic dystrophy knock-in mice is differentially affected by Msh3 and Msh6 mismatch-repair proteins
Hum. Mol. Genet., January 1, 2002; 11(2): 191 - 198.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
H. Seznec, O. Agbulut, N. Sergeant, C. Savouret, A. Ghestem, N. Tabti, J.-C. Willer, L. Ourth, C. Duros, E. Brisson, et al.
Mice transgenic for the human myotonic dystrophy region with expanded CTG repeats display muscular and brain abnormalities
Hum. Mol. Genet., November 1, 2001; 10(23): 2717 - 2726.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
N. Sergeant, B. Sablonniere, S. Schraen-Maschke, A. Ghestem, C.-A. Maurage, A. Wattez, P. Vermersch, and A. Delacourte
Dysregulation of human brain microtubule-associated tau mRNA maturation in myotonic dystrophy type 1
Hum. Mol. Genet., September 1, 2001; 10(19): 2143 - 2155.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
M. Gomes-Pereira, M. T. Fortune, and D. G. Monckton
Mouse tissue culture models of unstable triplet repeats: in vitro selection for larger alleles, mutational expansion bias and tissue specificity, but no association with cell division rates
Hum. Mol. Genet., April 1, 2001; 10(8): 845 - 854.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
M. Khajavi, A. M. Tari, N. B. Patel, K. Tsuji, D. R. Siwak, M. L. Meistrich, N. H. A. Terry, and T. Ashizawa
'Mitotic drive' of expanded CTG repeats in myotonic dystrophy type 1 (DM1)
Hum. Mol. Genet., April 1, 2001; 10(8): 855 - 863.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.