Animal models of Charcot-Marie-Tooth disease and their relevance for understanding the disease in humans

Charcot-Marie-Tooth neuropathies (CMT) are inherited neuromuscular disorders caused by length-dependent neurodegeneration of peripheral nerves. More than 900 mutations in 60 different genes are responsible for Charcot-Marie-Tooth neuropathy. Despite significant progress in therapeutic strategies, the disease remains incurable. The increasing number of genes linked to the disease, and their considerable clinical and genetic heterogeneity renders the development of these strategies particularly challenging. In this context, cellular and animals models provide powerful tools. Efficient motor and sensory tests have been developed to assess the behavioral phenotype in transgenic animal models (rodents and fly). When these models reproduce a phenotype comparable to CMT, they allow therapeutic approaches and the discovery of modifiers and biomarkers. The majority of these models concern the demyelinating form (type 1) of the disease. The axonal form (type 2) is less common. Both forms can further be divided into multiple subtypes reflecting the heterogeneity of the disease. In this review, we describe the most convincing transgenic rodent and fly models of CMT and how some of them led to clinical trials. (C) 2013 Elsevier Masson SAS. All rights reserved.