Skip Navigation


Human Molecular Genetics Advance Access originally published online on November 17, 2004
Human Molecular Genetics 2005 14(1):155-169; doi:10.1093/hmg/ddi017
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
14/1/155    most recent
ddi017v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (49)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Arimura, T.
Right arrow Articles by Bonne, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Arimura, T.
Right arrow Articles by Bonne, G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, Vol. 14, No. 1 © Oxford University Press 2005; all rights reserved

Mouse model carrying H222P-Lmna mutation develops muscular dystrophy and dilated cardiomyopathy similar to human striated muscle laminopathies

Takuro Arimura1,2,{dagger}, Anne Helbling-Leclerc1,2,{dagger}, Catherine Massart1,2, Shaida Varnous1,2, Florence Niel1,2, Emmanuelle Lacène1,2, Yves Fromes1,2, Marcel Toussaint3, Anne-Marie Mura4, Dagmar I. Keller1,2, Helge Amthor5, Richard Isnard2,6, Marie Malissen4, Ketty Schwartz1,2 and Gisèle Bonne1,2,*

1Inserm UR582, Institut de Myologie, GH Pitié-Salpêtrière, 75013 Paris, France, 2Inserm IFR14, GH Pitié-Salpêtrière, Paris, France, 3Service des Maladies Cardiovasculaires, Centre Hospitalier Général, 91160 Longjumeau, France, 4Centre d'Immunologie de Marseille-Luminy, Inserm-CNRS-Université de la Méditerranée, Parc Scientifique de Luminy, 13000 Marseille, France, 5Veterinary Basic Sciences, The Royal Veterinary College, London NW1 OTU, UK and 6Service de Cardiologie, GH Pitié-Salpêtrière, 75013 Paris, France

* To whom correspondence should be addressed at: Inserm UR582, Institut de Myologie, Bâtiment Babinski, Groupe Hospitalier Pitié-Salpétrière, 47 boulevard de l'Hôpital, 75651 Paris Cedex 13, France. Tel: +33 142165723; Fax: +33 142165700; Email: g.bonne{at}myologie.chups.jussieu.fr

Received September 30, 2004; Accepted November 5, 2004

Laminopathies are a group of disorders caused by mutations in the LMNA gene encoding A-type lamins, components of the nuclear lamina. Three of these disorders affect specifically the skeletal and/or cardiac muscles, and their pathogenic mechanisms are still unknown. We chose the LMNA H222P missense mutation identified in a family with autosomal dominant Emery–Dreifuss muscular dystrophy, one of the striated muscle-specific laminopathies, to create a faithful mouse model of this type of laminopathy. The mutant mice exhibit overtly normal embryonic development and sexual maturity. At adulthood, male homozygous mice display reduced locomotion activity with abnormal stiff walking posture and all of them die by 9 months of age. As for cardiac phenotype, they develop chamber dilation and hypokinesia with conduction defects. These abnormal skeletal and cardiac features were also observed in the female homozygous mice but with a later-onset than in males. Histopathological analysis of the mice revealed muscle degeneration with fibrosis associated with dislocation of heterochromatin and activation of Smad signalling in heart and skeletal muscles. These results demonstrate that LmnaH222P/H222P mice represent a good model for studying laminopathies affecting striated muscles as they develop a dystrophic condition of both skeletal and cardiac muscles similar to the human diseases.

{dagger} The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
Y. Wang, A. A. Panteleyev, D. M. Owens, K. Djabali, C. L. Stewart, and H. J. Worman
Epidermal expression of the truncated prelamin A causing Hutchinson-Gilford progeria syndrome: effects on keratinocytes, hair and skin
Hum. Mol. Genet., August 1, 2008; 17(15): 2357 - 2369.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
J. M. Holaska
Emerin and the Nuclear Lamina in Muscle and Cardiac Disease
Circ. Res., July 3, 2008; 103(1): 16 - 23.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
J. S. H. Lee, C. M. Hale, P. Panorchan, S. B. Khatau, J. P. George, Y. Tseng, C. L. Stewart, D. Hodzic, and D. Wirtz
Nuclear Lamin A/C Deficiency Induces Defects in Cell Mechanics, Polarization, and Migration
Biophys. J., October 1, 2007; 93(7): 2542 - 2552.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
A. Muchir, P. Pavlidis, G. Bonne, Y. K. Hayashi, and H. J. Worman
Activation of MAPK in hearts of EMD null mice: similarities between mouse models of X-linked and autosomal dominant Emery Dreifuss muscular dystrophy
Hum. Mol. Genet., August 1, 2007; 16(15): 1884 - 1895.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
B. C. Capell, F. S. Collins, and E. G. Nabel
Mechanisms of Cardiovascular Disease in Accelerated Aging Syndromes
Circ. Res., July 6, 2007; 101(1): 13 - 26.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
S. Spuler, T. Kalbhenn, J. Zabojszcza, F.K.H. van Landeghem, A. Ludtke, K. Wenzel, M. Koehnlein, M. Schuelke, L. Ludemann, and H. H. Schmidt
Muscle and nerve pathology in Dunnigan familial partial lipodystrophy
Neurology, February 27, 2007; 68(9): 677 - 683.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Lammerding, L. G. Fong, J. Y. Ji, K. Reue, C. L. Stewart, S. G. Young, and R. T. Lee
Lamins A and C but Not Lamin B1 Regulate Nuclear Mechanics
J. Biol. Chem., September 1, 2006; 281(35): 25768 - 25780.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
Y. Wang, A. J. Herron, and H. J. Worman
Pathology and nuclear abnormalities in hearts of transgenic mice expressing M371K lamin A encoded by an LMNA mutation causing Emery-Dreifuss muscular dystrophy
Hum. Mol. Genet., August 15, 2006; 15(16): 2479 - 2489.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
J. L. V. Broers, F. C. S. Ramaekers, G. Bonne, R. B. Yaou, and C. J. Hutchison
Nuclear lamins: laminopathies and their role in premature ageing.
Physiol Rev, July 1, 2006; 86(3): 967 - 1008.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
K. Manju, B. Muralikrishna, and V. K Parnaik
Expression of disease-causing lamin A mutants impairs the formation of DNA repair foci
J. Cell Sci., July 1, 2006; 119(13): 2704 - 2714.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Biol.Home page
D. Dorner, S. Vlcek, N. Foeger, A. Gajewski, C. Makolm, J. Gotzmann, C. J. Hutchison, and R. Foisner
Lamina-associated polypeptide 2{alpha} regulates cell cycle progression and differentiation via the retinoblastoma-E2F pathway.
J. Cell Biol., April 10, 2006; 173(1): 83 - 93.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
R. Ozawa, Y. K. Hayashi, M. Ogawa, R. Kurokawa, H. Matsumoto, S. Noguchi, I. Nonaka, and I. Nishino
Emerin-Lacking Mice Show Minimal Motor and Cardiac Dysfunctions with Nuclear-Associated Vacuoles
Am. J. Pathol., March 1, 2006; 168(3): 907 - 917.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
R. L. Frock, B. A. Kudlow, A. M. Evans, S. A. Jameson, S. D. Hauschka, and B. K. Kennedy
Lamin A/C and emerin are critical for skeletal muscle satellite cell differentiation.
Genes & Dev., February 15, 2006; 20(4): 486 - 500.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
G. Euler-Taimor and J. Heger
The complex pattern of SMAD signaling in the cardiovascular system
Cardiovasc Res, January 1, 2006; 69(1): 15 - 25.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
S. G. Young, L. G. Fong, and S. Michaelis
Thematic Review Series: Lipid Posttranslational Modifications. Prelamin A, Zmpste24, misshapen cell nuclei, and progeria--new evidence suggesting that protein farnesylation could be important for disease pathogenesis
J. Lipid Res., December 1, 2005; 46(12): 2531 - 2558.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. GenomicsHome page
I. Filesi, F. Gullotta, G. Lattanzi, M. R. D'Apice, C. Capanni, A. M. Nardone, M. Columbaro, G. Scarano, E. Mattioli, P. Sabatelli, et al.
Alterations of nuclear envelope and chromatin organization in mandibuloacral dysplasia, a rare form of laminopathy
Physiol Genomics, October 17, 2005; 23(2): 150 - 158.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
S. R. Schulze, B. Curio-Penny, Y. Li, R. A. Imani, L. Rydberg, P. K. Geyer, and L. L. Wallrath
Molecular Genetic Analysis of the Nested Drosophila melanogaster Lamin C Gene
Genetics, September 1, 2005; 171(1): 185 - 196.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
D. J. Milan and C. A. MacRae
Animal models for arrhythmias
Cardiovasc Res, August 15, 2005; 67(3): 426 - 437.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
L. C. Mounkes, S. V. Kozlov, J. N. Rottman, and C. L. Stewart
Expression of an LMNA-N195K variant of A-type lamins results in cardiac conduction defects and death in mice
Hum. Mol. Genet., August 1, 2005; 14(15): 2167 - 2180.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. H. Yang, M. O. Bergo, J. I. Toth, X. Qiao, Y. Hu, S. Sandoval, M. Meta, P. Bendale, M. H. Gelb, S. G. Young, et al.
Blocking protein farnesyltransferase improves nuclear blebbing in mouse fibroblasts with a targeted Hutchinson-Gilford progeria syndrome mutation
PNAS, July 19, 2005; 102(29): 10291 - 10296.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.