CTG trinucleotide repeat "big jumps": large expansions, small mice.

Full Abstract

Trinucleotide repeat expansions are the genetic cause of numerous human diseases, including fragile X mental retardation, Huntington disease, and myotonic dystrophy type 1. Disease severity and age of onset are critically linked to expansion size. Previous mouse models of repeat instability have not recreated large intergenerational expansions ("big jumps"), observed when the repeat is transmitted from one generation to the next, and have never attained the very large tract lengths possible in humans. Here, we describe dramatic intergenerational CTG*CAG repeat expansions of several hundred repeats in a transgenic mouse model of myotonic dystrophy type 1, resulting in increasingly severe phenotypic and molecular abnormalities. Homozygous mice carrying over 700 trinucleotide repeats on both alleles display severely reduced body size and splicing abnormalities, notably in the central nervous system. Our findings demonstrate that large intergenerational trinucleotide repeat expansions can be recreated in mice, and endorse the use of transgenic mouse models to refine our understanding of triplet repeat expansion and the resulting pathogenesis.

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Author information

Author/s: Gomes-Pereira, Mário (M); Foiry, Laurent (L); Nicole, Annie (A); Huguet, Aline (A); Junien, Claudine (C); Munnich, Arnold (A); Gourdon, Geneviève (G);

Affiliation: INSERM, U781, Hôpital Necker Enfants Malades, Paris, France.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: PLoS genetics (PLoS Genet), published in United States. (Language: eng)

Reference: 2007-Apr; vol 3 (issue 4) : pp e52

Dates: Created 2007/05/21; Completed 2007/06/11; Revised 2008/11/20;

PMID: 17411343, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Alleles
Animals
Base Sequence
Body Size - genetics
Genomic Instability - genetics
Homozygote

Humans
Mice
Mice, Inbred C57BL
Mice, Transgenic
RNA Splicing - genetics
Trinucleotide Repeat Expansion - genetics

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