A-type and B-type nuclear lamins form a family of nuclear envelope proteins that have an essential function in the maintenance of nuclear structure. Mutations in the human lamin A gene have been linked to several diseases which include Emery-Dreifuss muscular dystrophy (EDMD) and cardiomyopathy. Since the A-type lamins are found in majority of adult cell types it is extremely puzzling that defects in these proteins should be associated primarily with muscle specific disorders. The goal of this proposal is to elucidate the roles that individual lam in family members play in the organization of the cell nucleus and how in particular this relates to the maintenance of muscle integrity. The proposal will take advantage of mouse strains harboring targeted mutations in lamin genes, including a strain in which the lamin A gene has been deleted and which develops a disorder that closely resembles human EDMD. Inactivation of B-type lamin genes as well as the introduction of specific human disease-linked point mutations into the mouse lamin A gene will provide novel insight into the role of individual lamin proteins in nuclear organization and how this relates to disease processes in humans.
