title: Animal models of spinal muscular atrophy.
abstract: Spinal muscular atrophy, a common autosomal recessive motor neuron disorder, is caused by the loss of the survival motor neuron gene (SMN1). SMN2, a nearly identical copy gene, is present in all spinal muscular atrophy patients but differs by a critical nucleotide that alters exon 7 splicing efficiency. This results in low survival motor neuron protein levels, which are not enough to sustain motor neurons. SMN disruption has been undertaken in different organisms (yeast, nematode, fly, zebrafish, and mouse) in an attempt to model this disease and gain fundamental knowledge about the survival motor neuron protein. This review compares the various animal models generated to date and summarizes a research picture that reveals a pleiotropic role for survival motor neuron protein; this summary also points to unique requirements for survival motor neuron protein in motor neurons. It is hoped that these observations will aid in pointing towards complementary paths for therapeutic discovery research.
authors.affiliation: University of Utah, Eccles Institute of Human Genetics, Salt Lake City, Utah, USA.
authors.forename: Aloicia
authors.initials: A
authors.lastname: Schmid
authors.forename: Christine J
authors.initials: CJ
authors.lastname: DiDonato
mesh_terms: D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D019143:Evolution, Molecular; D006801:Humans; D007448:Invertebrates / Q000235:genetics / Q000378:metabolism; D008967:Molecular Biology / Q000379:methods / Q000639:trends*; D009134:Muscular Atrophy, Spinal / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D055532:SMN Complex Proteins; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein; D014714:Vertebrates / Q000235:genetics / Q000378:metabolism
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; 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; C526474:smn1 protein, zebrafish