Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
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 (52)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Cifuentes-Diaz, C.
Right arrow Articles by Melki, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cifuentes-Diaz, C.
Right arrow Articles by Melki, J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, 2002, Vol. 11, No. 12 1439-1447
© 2002 Oxford University Press

Neurofilament accumulation at the motor endplate and lack of axonal sprouting in a spinal muscular atrophy mouse model

Carmen Cifuentes-Diaz, Sophie Nicole, Maria E. Velasco, Christophe Borra-Cebrian, Cristina Panozzo, Tony Frugier, Gaelle Millet, Natacha Roblot, Vandana Joshi and Judith Melki*

Molecular Neurogenetics Laboratory, Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Evry, EMI-9913, GENOPOLE, 91057 Evry, France

Received February 7, 2002; Accepted March 27, 2002

Mutations of survival of the motor neuron gene (SMN1) are responsible for spinal muscular atrophy (SMA), a common genetic cause of death in childhood. The cellular mechanism by which mutations of SMN1 are responsible for the selective neuromuscular defect and motor neuron cell degeneration observed in SMA has not been described. We have previously generated mice carrying a homozygous deletion of Smn exon 7 directed to neurons. We report here that these mutant mice display a dramatic and progressive loss of motor axons involving both proximal and terminal regions, in agreement with the skeletal muscle denervation process and disease progression. Moreover, we found massive accumulation of neurofilaments, including phosphorylated forms, in terminal axons of the remaining neuromuscular junctions. This aberrant cytoskeletal organization of synaptic terminals was associated with reduction of branched structures of the postsynaptic apparatus and defect of axonal sprouting in mutant mice. Together, these findings may be responsible for severe motor neuron dysfunction, and suggest that loss of motor neuron cell bodies results from a ‘dying-back’ axonopathy in SMA. Smn mutant mice should represent a valuable model for elucidating the pathway linking Smn to cytoskeletal organization.

* To whom correspondence should be addressed at: Molecular Neurogenetics Laboratory, INSERM, Université d'Evry, EMI-9913, GENOPOLE, 2 rue Gaston Crémieux, CP5724, 91057 Evry, France. Tel: +33 1 6087 4552; Fax: +33 1 6087 4550; Email: j.melki{at}genopole.inserm.fr


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
M. E.R. Butchbach, J. Singh, M. Thorsteinsdottir, L. Saieva, E. Slominski, J. Thurmond, T. Andresson, J. Zhang, J. D. Edwards, L. R. Simard, et al.
Effects of 2,4-diaminoquinazoline derivatives on SMN expression and phenotype in a mouse model for spinal muscular atrophy
Hum. Mol. Genet., November 25, 2009; (2009) ddp510v2.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
L. M. Murray, S. Lee, D. Baumer, S. H. Parson, K. Talbot, and T. H. Gillingwater
Pre-symptomatic development of lower motor neuron connectivity in a mouse model of severe spinal muscular atrophy
Hum. Mol. Genet., November 11, 2009; (2009) ddp506v2.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
V. B. Mattis, A. D. Ebert, M. Y. Fosso, C.-W. Chang, and C. L. Lorson
Delivery of a read-through inducing compound, TC007, lessens the severity of a spinal muscular atrophy animal model
Hum. Mol. Genet., October 15, 2009; 18(20): 3906 - 3913.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
P.-C. Chen, L.-N. Qin, X.-M. Li, B. J. Walters, J. A. Wilson, L. Mei, and S. M. Wilson
The Proteasome-Associated Deubiquitinating Enzyme Usp14 Is Essential for the Maintenance of Synaptic Ubiquitin Levels and the Development of Neuromuscular Junctions
J. Neurosci., September 2, 2009; 29(35): 10909 - 10919.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
L. Kong, X. Wang, D. W. Choe, M. Polley, B. G. Burnett, M. Bosch-Marce, J. W. Griffin, M. M. Rich, and C. J. Sumner
Impaired Synaptic Vesicle Release and Immaturity of Neuromuscular Junctions in Spinal Muscular Atrophy Mice
J. Neurosci., January 21, 2009; 29(3): 842 - 851.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
S. Kariya, G.-H. Park, Y. Maeno-Hikichi, O. Leykekhman, C. Lutz, M. S. Arkovitz, L. T. Landmesser, and U. R. Monani
Reduced SMN protein impairs maturation of the neuromuscular junctions in mouse models of spinal muscular atrophy
Hum. Mol. Genet., August 15, 2008; 17(16): 2552 - 2569.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
L. M. Murray, L. H. Comley, D. Thomson, N. Parkinson, K. Talbot, and T. H. Gillingwater
Selective vulnerability of motor neurons and dissociation of pre- and post-synaptic pathology at the neuromuscular junction in mouse models of spinal muscular atrophy
Hum. Mol. Genet., April 1, 2008; 17(7): 949 - 962.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
D. A. Monks, J. A. Johansen, K. Mo, P. Rao, B. Eagleson, Z. Yu, A. P. Lieberman, S. M. Breedlove, and C. L. Jordan
Overexpression of wild-type androgen receptor in muscle recapitulates polyglutamine disease
PNAS, November 13, 2007; 104(46): 18259 - 18264.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
S. Jablonka, M. Beck, B. D. Lechner, C. Mayer, and M. Sendtner
Defective Ca2+ channel clustering in axon terminals disturbs excitability in motoneurons in spinal muscular atrophy
J. Cell Biol., October 8, 2007; 179(1): 139 - 149.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
T. Dunckley, M. J. Huentelman, D. W. Craig, J. V. Pearson, S. Szelinger, K. Joshipura, R. F. Halperin, C. Stamper, K. R. Jensen, D. Letizia, et al.
Whole-Genome Analysis of Sporadic Amyotrophic Lateral Sclerosis
N. Engl. J. Med., August 23, 2007; 357(8): 775 - 788.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
M. K. E. Schaefer, H. Schmalbruch, E. Buhler, C. Lopez, N. Martin, J.-L. Guenet, and G. Haase
Progressive Motor Neuronopathy: A Critical Role of the Tubulin Chaperone TBCE in Axonal Tubulin Routing from the Golgi Apparatus
J. Neurosci., August 15, 2007; 27(33): 8779 - 8789.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
J. van Bergeijk, K. Rydel-Konecke, C. Grothe, and P. Claus
The spinal muscular atrophy gene product regulates neurite outgrowth: importance of the C terminus
FASEB J, May 1, 2007; 21(7): 1492 - 1502.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
M. Katsuno, H. Adachi, M. Minamiyama, M. Waza, K. Tokui, H. Banno, K. Suzuki, Y. Onoda, F. Tanaka, M. Doyu, et al.
Reversible Disruption of Dynactin 1-Mediated Retrograde Axonal Transport in Polyglutamine-Induced Motor Neuron Degeneration.
J. Neurosci., November 22, 2006; 26(47): 12106 - 12117.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
C. Girard, H. Neel, E. Bertrand, and R. Bordonne
Depletion of SMN by RNA interference in HeLa cells induces defects in Cajal body formation
Nucleic Acids Res., May 31, 2006; 34(10): 2925 - 2932.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. GenomicsHome page
R. Olaso, V. Joshi, J. Fernandez, N. Roblot, S. Courageot, J. P. Bonnefont, and J. Melki
Activation of RNA metabolism-related genes in mouse but not human tissues deficient in SMN
Physiol Genomics, January 12, 2006; 24(2): 97 - 104.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
J. M. Vitte, B. Davoult, N. Roblot, M. Mayer, V. Joshi, S. Courageot, F. Tronche, J. Vadrot, M. H. Moreau, F. Kemeny, et al.
Deletion of Murine Smn Exon 7 Directed to Liver Leads to Severe Defect of Liver Development Associated with Iron Overload
Am. J. Pathol., November 1, 2004; 165(5): 1731 - 1741.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
K. Grohmann, W. Rossoll, I. Kobsar, B. Holtmann, S. Jablonka, C. Wessig, G. Stoltenburg-Didinger, U. Fischer, C. Hubner, R. Martini, et al.
Characterization of Ighmbp2 in motor neurons and implications for the pathomechanism in a mouse model of human spinal muscular atrophy with respiratory distress type 1 (SMARD1)
Hum. Mol. Genet., September 15, 2004; 13(18): 2031 - 2042.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
W. Rossoll, S. Jablonka, C. Andreassi, A.-K. Kroning, K. Karle, U. R. Monani, and M. Sendtner
Smn, the spinal muscular atrophy-determining gene product, modulates axon growth and localization of {beta}-actin mRNA in growth cones of motoneurons
J. Cell Biol., November 24, 2003; 163(4): 801 - 812.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
M. L. McWhorter, U. R. Monani, A. H.M. Burghes, and C. E. Beattie
Knockdown of the survival motor neuron (Smn) protein in zebrafish causes defects in motor axon outgrowth and pathfinding
J. Cell Biol., September 1, 2003; 162(5): 919 - 932.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
H. L. Zhang, F. Pan, D. Hong, S. M. Shenoy, R. H. Singer, and G. J. Bassell
Active Transport of the Survival Motor Neuron Protein and the Role of Exon-7 in Cytoplasmic Localization
J. Neurosci., July 23, 2003; 23(16): 6627 - 6637.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
Y. B. Chan, I. Miguel-Aliaga, C. Franks, N. Thomas, B. Trulzsch, D. B. Sattelle, K. E. Davies, and M. van den Heuvel
Neuromuscular defects in a Drosophila survival motor neuron gene mutant
Hum. Mol. Genet., June 15, 2003; 12(12): 1367 - 1376.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
J.-C. Lesbordes, C. Cifuentes-Diaz, A. Miroglio, V. Joshi, T. Bordet, A. Kahn, and J. Melki
Therapeutic benefits of cardiotrophin-1 gene transfer in a mouse model of spinal muscular atrophy
Hum. Mol. Genet., June 1, 2003; 12(11): 1233 - 1239.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
S. Nicole, B. Desforges, G. Millet, J. Lesbordes, C. Cifuentes-Diaz, D. Vertes, M. L. Cao, F. De Backer, L. Languille, N. Roblot, et al.
Intact satellite cells lead to remarkable protection against Smn gene defect in differentiated skeletal muscle
J. Cell Biol., May 12, 2003; 161(3): 571 - 582.
[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.