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

• Published in: Human molecular genetics 2000-03, Vol.9 (5), p.849-858
• Main Authors: FRUGIER, T, TIZIANO, F. D, CIFUENTES-DIAZ, C, MINIOU, P, ROBLOT, N, DIERICH, A, LE MEUR, M, MELKI, J
• Format: Article
• Language: English
• Subjects: Animal biology; Animals; Base Sequence; Biological and medical sciences; Cell Nucleus - metabolism; Cyclic AMP Response Element-Binding Protein; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Models, Animal; DNA Primers; Exons; Gene Deletion; Genes, Lethal; Homozygote; Life Sciences; Medical sciences; Mice; Motor Neurons - metabolism; Muscular Atrophy, Spinal - genetics; Muscular Atrophy, Spinal - metabolism; Nerve Tissue Proteins - chemistry; Nerve Tissue Proteins - genetics; Neurology; Phenotype; RNA-Binding Proteins; SMN Complex Proteins; SMN gene; SMN protein; spinal muscular atrophy
• ISSN: 0964-6906; 1460-2083; 1460-2083
• DOI: 10.1093/hmg/9.5.849

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.