Mouse Models of the Laminopathies

Colin Stewart

Serguei Kozlov

Loren Fong

Stephen Young

^{Laboratory of Cancer and Developmental Biology, National Cancer Institute, Frederick, Maryland, 21702}

^{Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095}

Address correspondence to Dr. Colin Stewart or to Dr. Stephen Young. Dr. Stewart’s address: Laboratory of Cancer and Developmental Biology, P.O. Box B, National Cancer Institute, Frederick, MD 21702, USA. Tel: (301) 846-1755; Fax: (301) 846-7117; E-mail: vog.frcficn@ctrawets. Dr. Young’s address: UCLA Dept of Medicine, Division of Cardiology, 650 Charles E. Young Dr. South, BH 307 CHS Bldg., Los Angeles, CA 90095. Tel: (310) 825-4934; Fax: (310) 206-0865; E-mail: ude.alcu.tendem@gnuoygs

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Abstract

The A and B type lamins are nuclear intermediate filament proteins that comprise the bulk of the nuclear lamina, a thin proteinaceous structure underlying the inner nuclear membrane. The A-type lamins are encoded by the lamin A gene (LMNA). Mutations in this gene have been linked to at least nine diseases, including the progeroid diseases Hutchinson-Gilford progeria and atypical Werner’s syndromes, striated muscle diseases including muscular dystrophies and dilated cardiomyopathies, lipodystrophies affecting adipose tissue deposition, diseases affecting skeletal development, and a peripheral neuropathy. To understand how different diseases arise from different mutations in the same gene, mouse lines carrying some of the same mutations found in the human diseases have been established. We, and others have generated mice with different mutations that result in progeria, muscular dystrophy, and dilated cardiomyopathy. To further our understanding of the functions of the lamins, we also created mice lacking lamin B1, as well as mice expressing only one of the A-type lamins. These mouse lines are providing insights into the functions of the lamina and how changes to the lamina affect the mechanical integrity of the nucleus as well as signaling pathways that, when disrupted, may contribute to the disease.

Keywords: Lamins, Nucleus, Laminopathies, Progeria

Abstract

Footnotes

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