title: Lamin B1 is required for mouse development and nuclear integrity.
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.
authors.affiliation: Veterans Affairs Greater Los Angeles Healthcare System, David Geffen School of Medicine, University of California, Los Angeles, CA 90073, USA.
authors.forename: Laurent
authors.initials: L
authors.lastname: Vergnes
authors.forename: Miklós
authors.initials: M
authors.lastname: Péterfy
authors.forename: Martin O
authors.initials: MO
authors.lastname: Bergo
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Young
authors.forename: Karen
authors.initials: K
authors.lastname: Reue
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000002:abnormalities; D002478:Cells, Cultured; D005314:Embryonic and Fetal Development / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D005804:Genes, Lethal; D034921:Lamin Type B / Q000235:genetics* / Q000378:metabolism*; D008168:Lung / Q000002:abnormalities; D051379:Mice; D018345:Mice, Knockout; D016254:Mutagenesis, Insertional; D034881:Nuclear Lamina / Q000473:pathology / Q000502:physiology*; D009999:Ossification, Heterotopic / Q000503:physiopathology; D013234:Stem Cells / Q000166:cytology
chemical_list: D034921:Lamin Type B