Mutated Lamin Gene Causes Muscular Dystrophy-Like Muscle Malformation in Worm Model

By introducing a mutation in the gene coding for lamin in a roundworm model, researchers have shown that the affected worms experience perturbed body muscle ultrastructure and reduced muscle function similar to that seen in humans suffering from Emery–Dreifuss muscular dystrophy (EDMD).

Most cases of Emery–Dreifuss muscular dystrophy are caused by mutations in the EMD gene. This gene provides instructions for making a protein called emerin, which appears to be essential for the normal function of skeletal and cardiac muscle. Less commonly, Emery–Dreifuss muscular dystrophy results from mutations in the LMNA gene. This gene provides instructions for making two very similar proteins, lamin A and lamin C. Most of the LMNA mutations that cause this condition result in the production of an altered version of these proteins.

To examine how lamin mutations cause EDMD investigators at the Hebrew University of Jerusalem (Israel) and their colleague from the Friedrich Miescher Institute for Biomedical Research (Basel, Switzerland) genetically engineered a population of roundworms (Caenorhabditis elegans) to express at low levels in otherwise wild-type worms a lamin carrying a point mutation, Y59C.

They reported in the September 29, 2011, online edition of the journal Current Biology that the worms carrying the point mutation had abnormal retention of a muscle-specific gene array at the nuclear periphery. This effect was specific to muscle and had no effect on other cells. These animals exhibited selectively perturbed body muscle structure and reduced muscle function, which resembled the situation in human EDMD patients.

Results of this study further showed that at the molecular level lamin was necessary for the perinuclear positioning of heterochromatin. Normal lamin filaments function to position silent genes at the nuclear periphery and allow release of the activated normal gene. Failure to so results in muscular deformation in the worm that is highly reminiscent of human EDMD.

Related Links:
Hebrew University of Jerusalem
Friedrich Miescher Institute for Biomedical Research