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 the inner nuclear membrane and represents an important determinant of interphase nuclear architecture. Its major components are the A- and B-type lamins. Whereas B-type lamins are found in all mammalian cells, A-type lamin exp...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of cell biology 1999-11, Vol.147 (5), p.913-919
Main Authors: Sullivan, Teresa, Escalante-Alcalde, Diana, Bhatt, Harshida, Anver, Miriam, Bhat, Narayan, Nagashima, Kunio, Stewart, Colin L., Burke, Brian
Format: Article
Language:English
Subjects:
Animals
Antibodies
Brief Report
Brief Reports
Cell nucleus
Cells
Cellular biology
Embryonic stem cells
emerin
Emery-Dreifuss muscular dystrophy
Fibroblasts - pathology
Gene Targeting
Genetic Carrier Screening
Hepatocytes
Homozygote
Humans
Immunohistochemistry
Lamins
Mice
Mice, Inbred C57BL
Mice, Knockout
Muscular dystrophies
Muscular Dystrophies - embryology
Muscular Dystrophies - genetics
Muscular Dystrophies - pathology
Muscular dystrophy
Mutagenesis, Site-Directed
Nuclear Envelope - metabolism
Nuclear Envelope - pathology
Nuclear membrane
Nuclear Proteins - biosynthesis
Nuclear Proteins - deficiency
Nuclear Proteins - genetics
Proteins
Sequence Deletion
Somatic cells
Transfection
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The nuclear lamina is a protein meshwork lining the nucleoplasmic face of the inner nuclear membrane and represents an important determinant of interphase nuclear architecture. Its major components are the A- and B-type lamins. Whereas B-type lamins are found in all mammalian cells, A-type lamin expression is developmentally regulated. In the mouse, A-type lamins do not appear until midway through embryonic development, suggesting that these proteins may be involved in the regulation of terminal differentiation. Here we show that mice lacking A-type lamins develop to term with no overt abnormalities. However, their postnatal growth is severely retarded and is characterized by the appearance of muscular dystrophy. This phenotype is associated 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 exhibit tissue-specific alterations to their nuclear envelope integrity and emerin distribution. In skeletal and cardiac muscles, this is manifest as dystrophic condition related to EDMD.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.147.5.913