title: Nuclear envelope alterations in fibroblasts from patients with muscular dystrophy, cardiomyopathy, and partial lipodystrophy carrying lamin A/C gene mutations.
abstract: 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.
authors.affiliation: INSERM U582, Institut de Myologie, GH Pitié-Salpêtrière, Bâtiment Babinski, 47 boulevard de l'Hôpital, Paris 75013, France.
authors.forename: A
authors.initials: A
authors.lastname: Muchir
authors.forename: J
authors.initials: J
authors.lastname: Medioni
authors.forename: M
authors.initials: M
authors.lastname: Laluc
authors.forename: C
authors.initials: C
authors.lastname: Massart
authors.forename: T
authors.initials: T
authors.lastname: Arimura
authors.forename: A J
authors.initials: AJ
authors.lastname: van der Kooi
authors.forename: I
authors.initials: I
authors.lastname: Desguerre
authors.forename: M
authors.initials: M
authors.lastname: Mayer
authors.forename: X
authors.initials: X
authors.lastname: Ferrer
authors.forename: S
authors.initials: S
authors.lastname: Briault
authors.forename: M
authors.initials: M
authors.lastname: Hirano
authors.forename: H J
authors.initials: HJ
authors.lastname: Worman
authors.forename: A
authors.initials: A
authors.lastname: Mallet
authors.forename: M
authors.initials: M
authors.lastname: Wehnert
authors.forename: K
authors.initials: K
authors.lastname: Schwartz
authors.forename: G
authors.initials: G
authors.lastname: Bonne
mesh_terms: D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D009202:Cardiomyopathies / Q000235:genetics* / Q000473:pathology; D002452:Cell Count; D002467:Cell Nucleus / Q000473:pathology; D002648:Child; D005260:Female; D005347:Fibroblasts / Q000473:pathology*; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D008060:Lipodystrophy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009136:Muscular Dystrophies / Q000235:genetics* / Q000473:pathology; D009154:Mutation / Q000235:genetics / Q000502:physiology; D009685:Nuclear Envelope / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins; D010641:Phenotype; D013946:Thymopoietins / Q000235:genetics
chemical_list: D034904:Lamin Type A; D008565:Membrane Proteins; D009687:Nuclear Proteins; D013946:Thymopoietins; C092710:emerin; C440308:lamin C