Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
Aging Cell. 2013 Feb;12(1):2-10. doi: 10.1111/acel.12021. Epub 2012 Nov 26.
The A- and B-type lamins are nuclear intermediate filament proteins in eukaryotic cells with a broad range of functions, including the organization of nuclear architecture and interaction with proteins in many cellular functions. Over 180 disease-causing mutations, termed 'laminopathies,' have been mapped throughout LMNA, the gene for A-type lamins in humans. Laminopathies can range from muscular dystrophies, cardiomyopathy, to Hutchinson-Gilford progeria syndrome. A number of mouse lines carrying some of the same mutations as those resulting in human diseases have been established. These LMNA-related mouse models have provided valuable insights into the functions of lamin A biogenesis and the roles of individual A-type lamins during tissue development. This review groups these LMNA-related mouse models into three categories: null mutants, point mutants, and progeroid mutants. We compare their phenotypes and discuss their potential implications in laminopathies and aging.
A 型和 B 型核纤层蛋白是真核细胞中的核中间丝蛋白，具有广泛的功能，包括核结构的组织和与许多细胞功能的蛋白质相互作用。在编码 A 型核纤层蛋白的基因 LMNA 中，已经发现了超过 180 种致病突变，称为“核纤层病”。核纤层病的范围从肌肉营养不良、心肌病到哈钦森-吉尔福德早衰综合征不等。已经建立了许多携带与导致人类疾病相同突变的小鼠品系。这些与 LMNA 相关的小鼠模型为核纤层 A 生物发生的功能以及在组织发育过程中各个 A 型核纤层蛋白的作用提供了有价值的见解。本综述将这些与 LMNA 相关的小鼠模型分为三类：缺失突变体、点突变体和早衰突变体。我们比较了它们的表型，并讨论了它们在核纤层病和衰老中的潜在意义。
