Abstract

The muscle disease field has benefited enormously from the increasing availability of genomic resources derived from the human genome mapping and allied projects. Although a number of skeletal and cardiac disorders are still at the linkage or candidate gene analysis stage, genes have been identified for the most common ones. The increasing variety of genes involved makes genetic screens an essential tool for more precise diagnosis and better classification of these disorders. The mouse represents the system of choice for the study of muscular dystrophies and cardiomyopathies but, not surprisingly, many murine models often show phenotypic differences between human and mouse. Only a handful of spontaneous or targeted mouse mutants are available within the field of muscle diseases compared to the increasing genetic complexity of myopathies and cardiomyopathies identified in humans. This shortage has been identified in other inherited diseases and has contributed to the revival of ENU (ethylnitrosourea) mutagenesis. Several large-scale ENU mutagenesis programs set up worldwide should provide allelic collections of mutants for pathologically interesting genes and uncover new gene functions. An effective integration between high throughput production of mutants, DNA-chip based expression analysis and the comprehensive maps derived from the human and mouse genome projects will make possible systematic studies of mammalian gene function, facilitating the identification of better mouse models.

Keywords: Muscle Diseases, Dystrophin glycoprotein complex DGC, Limb girdle Muscular dystrophy LGMD, Muscular dystrophy CMD, Cardiomyopathies, Mutagenesis, Muscle lim protein MLP