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Göteborgs universitets publikationer

Lamin B1 is required for mouse development and nuclear integrity

Författare och institution:
L. Vergnes (-); M. Peterfy (-); Martin Bergö (Institutionen för invärtesmedicin); S. G. Young (-); K. Reue (-)
Publicerad i:
Proc Natl Acad Sci U S A, 101 ( 28 ) s. 10428-10433
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
Lamins are key structural components of the nuclear lamina, an intermediate filament meshwork that lies beneath the inner nuclear membrane. Lamins play a role in nuclear architecture, DNA replication, and gene expression. Mutations affecting A-type lamins have been associated with a variety of human diseases, including muscular dystrophy, cardiomyopathy, lipodystrophy, and progeria, but mutations in B-type lamins have never been identified in humans or in experimental animals. To investigate the in vivo function of lamin B1, the major B-type lamin, we generated mice with an insertional mutation in Lmnb1. The mutation resulted in the synthesis of a mutant lamin B1 protein lacking several key functional domains, including a portion of the rod domain, the nuclear localization signal, and the CAAX motif (the carboxyl-terminal signal for farnesylation). Homozygous Lmnb1 mutant mice survived embryonic development but died at birth with defects in lung and bone. Fibroblasts from mutant embryos grew under standard cell-culture conditions but displayed grossly misshapen nuclei, impaired differentiation, increased polyploidy, and premature senescence. Thus, the lamin B1 mutant mice provide evidence for a broad and nonredundant function of lamin B1 in mammalian development. These mutant mice and cell lines derived from them will be useful models for studying the role of the nuclear lamina in various cellular processes.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Medicinska grundvetenskaper ->
Cell- och molekylärbiologi ->
Patologi ->
Molekylär medicin
Djurmodeller, CAAX proteiner, Animals, Bone and Bones/abnormalities, Cells, Cultured, Embryonic and Fetal Development/physiology, Fibroblasts/cytology, *Gene Expression Regulation, Developmental, Genes, Lethal, Lamin Type B/*genetics/*metabolism, Lung/abnormalities, Mice, Mice, Knockout, Mutagenesis, Insertional, Nuclear Lamina/pathology/*physiology, Ossification, Heterotopic/physiopathology, Research Support, U.S. Gov't, P.H.S., Stem Cells/cytology
Postens nummer:
Posten skapad:
2007-10-18 15:37

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