Nuclear targeting defect of SMN lacking the C-terminus in a mouse model of spinal muscular atrophy

被引:186
作者
Frugier, T [1 ]
Tiziano, FD [1 ]
Cifuentes-Diaz, C [1 ]
Miniou, P [1 ]
Roblot, N [1 ]
Dierich, A [1 ]
Le Meur, M [1 ]
Melki, J [1 ]
机构
[1] ULP, CNRS, INSERM, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, CU Strasbourg, France
关键词
D O I
10.1093/hmg/9.5.849
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 Delta 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.
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页码:849 / 858
页数:10
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