Nuclear targeting defect of SMN lacking the C-terminus in a mouse model of spinal muscular atrophy.
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 (SMNDeltaC15) 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.
Frugier
T
T
Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM, CNRS, ULP, BP163, 67404 Illkirch cedex, CU de Strasbourg, France.
Tiziano
F D
FD
Cifuentes-Diaz
C
C
Miniou
P
P
Roblot
N
N
Dierich
A
A
Le Meur
M
M
Melki
J
J
D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein; D017931:DNA Primers; D004195:Disease Models, Animal; D005091:Exons; D017353:Gene Deletion; D005804:Genes, Lethal; D006720:Homozygote; D051379:Mice; D009046:Motor Neurons / Q000378:metabolism; D009134:Muscular Atrophy, Spinal / Q000235:genetics* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics*; D010641:Phenotype; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins
D017362:Cyclic AMP Response Element-Binding Protein; D017931:DNA Primers; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins