Sökning: WFRF:(Bergö Martin) >
Prelamin A and lami...
Prelamin A and lamin A appear to be dispensable in the nuclear lamina
-
Fong, L. G. (författare)
-
Ng, J. K. (författare)
-
Lammerding, J. (författare)
-
visa fler...
-
Vickers, T. A. (författare)
-
Meta, M. (författare)
-
Cote, N. (författare)
-
Gavino, B. (författare)
-
Qiao, X. (författare)
-
Chang, S. Y. (författare)
-
Young, S. R. (författare)
-
Yang, S. H. (författare)
-
Stewart, C. L. (författare)
-
Lee, R. T. (författare)
-
Bennett, C. F. (författare)
-
- Bergö, Martin, 1970 (författare)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för invärtesmedicin,Wallenberg Laboratory,Institute of Medicine, Department of Internal Medicine
-
Young, S. G. (författare)
-
visa färre...
-
(creator_code:org_t)
- 2006
- 2006
- Engelska.
-
Ingår i: J Clin Invest. ; 116:3, s. 743-752
- Relaterad länk:
-
https://gup.ub.gu.se...
Abstract
Ämnesord
Stäng
- 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(LCO/LCO)), which produce lamin C but no lamin A or prelamin A (the precursor to lamin A). Lmna(LCO/LCO) mice were entirely healthy, and Lmna(LCO/LCO) 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 Lmna(LCO) 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- Djurmodeller
- CAAX proteiner
- prelamin A
- Animals
- Cell Line
- Transformed
- Cells
- Cultured
- Female
- Fibroblasts/metabolism
- Lamin Type A/deficiency/genetics/metabolism/*physiology
- Mice
- Mice
- Inbred C57BL
- Mice
- Knockout
- Mice
- Transgenic
- Muscle Weakness/genetics
- Nuclear Lamina/*physiology
- Nuclear Proteins/genetics/*physiology
- Protein Isoforms/genetics/metabolism
- Protein Precursors/genetics/*physiology
- RNA
- Messenger/metabolism
- Research Support
- N.I.H.
- Extramural
- Research Support
- Non-U.S. Gov't
- Skull/abnormalities
- Spine/abnormalities
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Fong, L. G.
-
Ng, J. K.
-
Lammerding, J.
-
Vickers, T. A.
-
Meta, M.
-
Cote, N.
-
visa fler...
-
Gavino, B.
-
Qiao, X.
-
Chang, S. Y.
-
Young, S. R.
-
Yang, S. H.
-
Stewart, C. L.
-
Lee, R. T.
-
Bennett, C. F.
-
Bergö, Martin, 1 ...
-
Young, S. G.
-
visa färre...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Medicinska och f ...
-
och Cell och molekyl ...
- Artiklar i publikationen
- J Clin Invest
- Av lärosätet
-
Göteborgs universitet