Loss of A-type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy

The nuclear lamina is a protein meshwork lining the nucleoplasmic face of t he inner nuclear membrane and represents an important determinant of interp hase nuclear architecture. Its major components are the A- and B-type lamin s. Whereas B-type lamins are found in all mammalian cells, A-type lamin exp ression is developmentally regulated, In the mouse, A-type lamins do not ap pear until midway through embryonic development, suggesting that these prot eins may be involved in the regulation of terminal differentiation. Here we show that mice lacking A-type lamins develop to term with no overt abnorma lities. However, their postnatal growth is severely retarded and is charact erized by the appearance of muscular dystrophy. This phenotype is associate d with ultrastructural perturbations to the nuclear envelope. These include the mislocalization of emerin, an inner nuclear membrane protein, defects in which are implicated in Emery-Dreifuss muscular dystrophy (EDMD), one of the three major X-linked dystrophies. Mice lacking the A-type lamins exhib it tissue-specific alterations to their nuclear envelope integrity and emer in distribution. In skeletal and cardiac muscles, this is manifest as a dys trophic condition related to EDMD.