Human Molecular Genetics, 2000, Vol. 9, No. 5 849-858
© 2000 Oxford University Press
Nuclear targeting defect of SMN lacking the C-terminus in a mouse model of spinal muscular atrophy
Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM, CNRS, ULP, BP163, 67404 Illkirch cedex, CU de Strasbourg, France
Deletion of the murine survival of motor neuron gene (SMN) exon 7, the most frequent mutation found in spinal muscular atrophy (SMA) patients, directed to neurons but not to skeletal muscle, enabled generation of a mouse model of SMA providing evidence that motor neurons are the primary target of the gene defect. Moreover, the mutated SMN protein (SMN
C15) is dramatically reduced in the motor neuron nuclei and causes a lack of gems associated with large aggregates of coilin, a coiled-body-specific protein. These results identify the lack of the nuclear targeting of SMN as the biochemical defect in SMA.
+ These authors contributed equally to this work
§ Present address: Laboratoire de Neurogénétique Moléculaire, INSERM E9913, GENOPOLE, 2 rue Gaston Crémieux CP 5724, 91057 Evry cedex, France
¶ To whom correspondence should be addressed. Tel: +33 1 60 87 45 52; Fax: +33 1 60 87 45 50; Email: j.melki@genopole.inserm.fr
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|
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|
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|
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|
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|
|
|
|
|
|
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|
|
|
|
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|
|
|
|
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|
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|
|
|
|
|
|
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|
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|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
S. Vyas, C. Bechade, B. Riveau, J. Downward, and A. Triller Involvement of survival motor neuron (SMN) protein in cell death Hum. Mol. Genet., October 15, 2002; 11(22): 2751 - 2764. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Massenet, L. Pellizzoni, S. Paushkin, I. W. Mattaj, and G. Dreyfuss The SMN Complex Is Associated with snRNPs throughout Their Cytoplasmic Assembly Pathway Mol. Cell. Biol., September 15, 2002; 22(18): 6533 - 6541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Fan and L. R. Simard Survival motor neuron (SMN) protein: role in neurite outgrowth and neuromuscular maturation during neuronal differentiation and development Hum. Mol. Genet., July 1, 2002; 11(14): 1605 - 1614. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Soler-Botija, I. Ferrer, I. Gich, M. Baiget, and F. Tizzano Neuronal death is enhanced and begins during foetal development in type I spinal muscular atrophy spinal cord Brain, July 1, 2002; 125(7): 1624 - 1634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
C. J. DiDonato, C. L. Lorson, Y. De Repentigny, L. Simard, C. Chartrand, E. J. Androphy, and R. Kothary Regulation of murine survival motor neuron (Smn) protein levels by modifying Smn exon 7 splicing Hum. Mol. Genet., November 1, 2001; 10(23): 2727 - 2736. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Hebert, P. W. Szymczyk, K. B. Shpargel, and A. G. Matera Coilin forms the bridge between Cajal bodies and SMN, the Spinal Muscular Atrophy protein Genes & Dev., October 15, 2001; 15(20): 2720 - 2729. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Cifuentes-Diaz, T. Frugier, F. D. Tiziano, E. Lacene, N. Roblot, V. Joshi, M. H. Moreau, and J. Melki Deletion of Murine SMN Exon 7 Directed to Skeletal Muscle Leads to Severe Muscular Dystrophy J. Cell Biol., March 5, 2001; 152(5): 1107 - 1114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Jablonka, M. Bandilla, S. Wiese, D. Buhler, B. Wirth, M. Sendtner, and U. Fischer Co-regulation of survival of motor neuron (SMN) protein and its interactor SIP1 during development and in spinal muscular atrophy Hum. Mol. Genet., March 1, 2001; 10(5): 497 - 505. [Abstract] [Full Text] [PDF]
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|
|
|
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L. Pellizzoni, B. Charroux, J. Rappsilber, M. Mann, and G. Dreyfuss A Functional Interaction between the Survival Motor Neuron Complex and RNA Polymerase II J. Cell Biol., January 8, 2001; 152(1): 75 - 86. [Abstract] [Full Text] [PDF]
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|
|
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D. A. Kerr, J. P. Nery, R. J. Traystman, B. N. Chau, and J. M. Hardwick Survival motor neuron protein modulates neuron-specific apoptosis PNAS, November 8, 2000; (2000) 230364197. [Abstract] [Full Text]
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P. J. Young, N. t. Man, C. L. Lorson, T. T. Le, E. J. Androphy, A. H.M. Burghes, and G. E. Morris The exon 2b region of the spinal muscular atrophy protein, SMN, is involved in self-association and SIP1 binding Hum. Mol. Genet., November 1, 2000; 9(19): 2869 - 2877. [Abstract] [Full Text] [PDF]
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U. R. Monani, D. D. Coovert, and A. H.M. Burghes Animal models of spinal muscular atrophy Hum. Mol. Genet., October 1, 2000; 9(16): 2451 - 2457. [Abstract] [Full Text] [PDF]
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 |
|
 J. Wang and G. Dreyfuss A Cell System with Targeted Disruption of the SMN Gene. FUNCTIONAL CONSERVATION OF THE SMN PROTEIN AND DEPENDENCE OF Gemin2 ON SMN J. Biol. Chem., March 23, 2001; 276(13): 9599 - 9605. [Abstract] [Full Text] [PDF]
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|
|
|
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J. Wang and G. Dreyfuss Characterization of Functional Domains of the SMN Protein in Vivo J. Biol. Chem., November 21, 2001; 276(48): 45387 - 45393. [Abstract] [Full Text] [PDF]
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D. A. Kerr, J. P. Nery, R. J. Traystman, B. N. Chau, and J. M. Hardwick Survival motor neuron protein modulates neuron-specific apoptosis PNAS, November 21, 2000; 97(24): 13312 - 13317. [Abstract] [Full Text] [PDF]
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