Mouse models of triplet repeat diseases

Triplet repeat expansions were first discovered in 1991 and since then have been found to be the mutation underlying a range of neurodegenerative, neuromuscular, and cognitive disorders including fragile X syndrome, myotonic dystrophy, Friedreich's ataxia, and the poly-glutamine disorders that include Huntington's disease. The repeats exert their detrimental effects through different molecular mechanisms dependent on whether the are located in coding or noncoding regions of the gene in question. During the past 10 yr, a wide range of strategies have been used to successfully establish mouse models for all of these disorders. This review presents an overview of these mouse models, discusses the insights into the molecular patho-genesis of these disorders that have been gained from their analysis and the strategies that are being used to uncover novel therapeutic options.