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Nuclear envelope alterations in fibroblasts from patients with muscular dystrophy, cardiomyopathy, and partial lipodystrophy carrying lamin A/C gene mutations
Author(s) -
Muchir A.,
Medioni J.,
Laluc M.,
Massart C.,
Arimura T.,
Kooi A. J. Van Der,
Desguerre I.,
Mayer M.,
Ferrer X.,
Briault S.,
Hirano M.,
Worman H. J.,
Mallet A.,
Wehnert M.,
Schwartz K.,
Bonne G.
Publication year - 2004
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.20122
Subject(s) - lamin , lmna , nuclear lamina , muscular dystrophy , progeria , biology , emerin , haploinsufficiency , premature aging , inner membrane , gene mutation , mutation , pathology , genetics , microbiology and biotechnology , cancer research , nuclear protein , gene , medicine , phenotype , transcription factor , mitochondrion
Mutations in LMNA , the gene that encodes nuclear lamins A and C, cause up to eight different diseases collectively referred to as “laminopathies.” These diseases affect striated muscle, adipose tissue, peripheral nerve, and bone, or cause features of premature aging. We investigated the consequences of LMNA mutations on nuclear architecture in skin fibroblasts from 13 patients with different laminopathies. Western‐blotting showed that none of the mutations examined led to a decrease in cellular levels of lamin A or C. Regardless of the disease, we observed honeycomb nuclear structures and nuclear envelope blebs in cells examined by immunofluorescence microscopy. Concentrated foci of lamin A/C in the nucleoplasm were also observed. Only mutations in the head and tail domains of lamins A and C significantly altered the nuclear architecture of patient fibroblasts. These results confirm that mutations in lamins A and C may lead to a weakening of a structural support network in the nuclear envelope in fibroblasts and that nuclear architecture changes depend upon the location of the mutation in different domains of lamin A/C. Muscle Nerve 30: 444–450, 2004