Abstract
Spinal muscular atrophy (SMA) is caused by deletion or specific mutations of the telomeric survival motor neuron ( SMN ) gene on human chromosome 5. The human SMN gene, in contrast to the Smn gene in mouse, is duplicated and the centromeric copy on chromosome 5 codes for transcripts which preferentially lead to C-terminally truncated SMN protein. Here we show that a 46% reduction of Smn protein levels in the spinal cord of Smn heterozygous mice leads to a marked loss of the cytoplasmic Smn pool and motor neuron degeneration resembling spinal muscular atrophy type 3. Smn heterozygous mice described here thus represent a model for the human disease. These mice could allow screening for SMA therapies and help in gaining further understanding of the pathophysiological events leading to motor neuron degeneration in SMA.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Blotting, Western
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Cyclic AMP Response Element-Binding Protein
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Disease Models, Animal
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Gene Dosage
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Humans
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Immunohistochemistry
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Mice
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Mice, Inbred C57BL
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Motor Neurons / metabolism
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Motor Neurons / pathology
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Nerve Tissue Proteins / genetics*
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Nerve Tissue Proteins / metabolism
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Phrenic Nerve / pathology
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RNA Splicing
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RNA, Messenger / analysis
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RNA-Binding Proteins
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Reverse Transcriptase Polymerase Chain Reaction
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SMN Complex Proteins
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Sciatic Nerve / pathology
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Spinal Cord / metabolism
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Spinal Muscular Atrophies of Childhood / genetics*
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Spinal Muscular Atrophies of Childhood / metabolism
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Spinal Muscular Atrophies of Childhood / pathology
Substances
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Cyclic AMP Response Element-Binding Protein
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Nerve Tissue Proteins
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RNA, Messenger
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RNA-Binding Proteins
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SMN Complex Proteins