title: A mouse model for spinal muscular atrophy.
abstract: The survival motor neuron gene is present in humans in a telomeric copy, SMN1, and several centromeric copies, SMN2. Homozygous mutation of SMN1 is associated with proximal spinal muscular atrophy (SMA), a severe motor neuron disease characterized by early childhood onset of progressive muscle weakness. To understand the functional role of SMN1 in SMA, we produced mouse lines deficient for mouse Smn and transgenic mouse lines that expressed human SMN2. Smn-/- mice died during the peri-implantation stage. In contrast, transgenic mice harbouring SMN2 in the Smn-/- background showed pathological changes in the spinal cord and skeletal muscles similar to those of SMA patients. The severity of the pathological changes in these mice correlated with the amount of SMN protein that contained the region encoded by exon 7. Our results demonstrate that SMN2 can partially compensate for lack of SMN1. The variable phenotypes of Smn-/-SMN2 mice reflect those seen in SMA patients, providing a mouse model for this disease.
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
authors.forename: H M
authors.initials: HM
authors.lastname: Hsieh-Li
authors.forename: J G
authors.initials: JG
authors.lastname: Chang
authors.forename: Y J
authors.initials: YJ
authors.lastname: Jong
authors.forename: M H
authors.initials: MH
authors.lastname: Wu
authors.forename: N M
authors.initials: NM
authors.lastname: Wang
authors.forename: C H
authors.initials: CH
authors.lastname: Tsai
authors.forename: H
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein; D017931:DNA Primers; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009134:Muscular Atrophy, Spinal / Q000235:genetics* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055532:SMN Complex Proteins; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein; D019076:Transgenes
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D017931:DNA Primers; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526471:SMN1 protein, human; C526477:SMN2 protein, human; C526472:Smn1 protein, mouse; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein