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Citations to this article

Prelamin A and lamin A appear to be dispensable in the nuclear lamina
Loren G. Fong, … , Martin O. Bergo, Stephen G. Young
Loren G. Fong, … , Martin O. Bergo, Stephen G. Young
Published March 1, 2006
Citation Information: J Clin Invest. 2006;116(3):743-752. https://doi.org/10.1172/JCI27125.
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Research Article Genetics Article has an altmetric score of 7

Prelamin A and lamin A appear to be dispensable in the nuclear lamina

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Abstract

Lamin A and lamin C, both products of Lmna, are key components of the nuclear lamina. In the mouse, a deficiency in both lamin A and lamin C leads to slow growth, muscle weakness, and death by 6 weeks of age. Fibroblasts deficient in lamins A and C contain misshapen and structurally weakened nuclei, and emerin is mislocalized away from the nuclear envelope. The physiologic rationale for the existence of the 2 different Lmna products lamin A and lamin C is unclear, although several reports have suggested that lamin A may have particularly important functions, for example in the targeting of emerin and lamin C to the nuclear envelope. Here we report the development of lamin C–only mice (Lmna+/+), which produce lamin C but no lamin A or prelamin A (the precursor to lamin A). Lmna+/+ mice were entirely healthy, and Lmna+/+ cells displayed normal emerin targeting and exhibited only very minimal alterations in nuclear shape and nuclear deformability. Thus, at least in the mouse, prelamin A and lamin A appear to be dispensable. Nevertheless, an accumulation of farnesyl–prelamin A (as occurs with a deficiency in the prelamin A processing enzyme Zmpste24) caused dramatically misshapen nuclei and progeria-like disease phenotypes. The apparent dispensability of prelamin A suggested that lamin A–related progeroid syndromes might be treated with impunity by reducing prelamin A synthesis. Remarkably, the presence of a single LmnaLCO allele eliminated the nuclear shape abnormalities and progeria-like disease phenotypes in Zmpste24–/– mice. Moreover, treating Zmpste24–/– cells with a prelamin A–specific antisense oligonucleotide reduced prelamin A levels and significantly reduced the frequency of misshapen nuclei. These studies suggest a new therapeutic strategy for treating progeria and other lamin A diseases.

Authors

Loren G. Fong, Jennifer K. Ng, Jan Lammerding, Timothy A. Vickers, Margarita Meta, Nathan Coté, Bryant Gavino, Xin Qiao, Sandy Y. Chang, Stephanie R. Young, Shao H. Yang, Colin L. Stewart, Richard T. Lee, C. Frank Bennett, Martin O. Bergo, Stephen G. Young

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 Total
Citations: 1 4 7 4 8 4 7 8 3 7 4 10 3 10 8 6 5 10 6 3 118
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2015 (4)

Title and authors Publication Year
Mice that express farnesylated versions of prelamin A in neurons develop achalasia
SH Yang, S Procaccia, HJ Jung, C Nobumori, A Tatar, Y Tu, YR Bayguinov, SJ Hwang, D Tran, SM Ward, LG Fong, SG Young
Human Molecular Genetics 2015
Directed targeting of chromatin to the nuclear lamina is mediated by chromatin state and A-type lamins
JC Harr, TR Luperchio, X Wong, E Cohen, SJ Wheelan, KL Reddy
The Journal of Cell Biology 2015
The tail domain of lamin B1 is more strongly modulated by divalent cations than lamin A
S Ganesh, Z Qin, ST Spagnol, MT Biegler, KA Coffey, A Kalinowski, MJ Buehler, KN Dahl
Nucleus 2015
A high-content imaging-based screening pipeline for the systematic identification of anti-progeroid compounds
N Kubben, KR Brimacombe, M Donegan, Z Li, T Misteli
Methods 2015

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ISSN: 0021-9738 (print), 1558-8238 (online)

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