title: Molecular mechanisms and animal models of spinal muscular atrophy.
abstract: Spinal muscular atrophy (SMA), the leading genetic cause of infant mortality, is characterized by the degeneration of spinal motor neurons and muscle atrophy. Although the genetic cause of SMA has been mapped to the Survival Motor Neuron1 (SMN1) gene, mechanisms underlying selective motor neuron degeneration in SMA remain largely unknown. Here we review the latest developments and our current understanding of the molecular mechanisms underlying SMA pathogenesis, focusing on the animal model systems that have been developed, as well as new diagnostic and treatment strategies that have been identified using these model systems. This article is part of a special issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.
authors.affiliation: Departments of Pediatrics, Neurology and Physiology, Northwestern University Feinberg School of Medicine, Lurie Children's Hospital of Chicago Research Center, IL 60611, Chicago.
authors.forename: Brittany M
authors.initials: BM
authors.lastname: Edens
authors.affiliation: Northwestern University Feinberg School of Medicine, IL 60611, Chicago.
authors.forename: Senda
authors.initials: S
authors.lastname: Ajroud-Driss
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, China.
authors.forename: Long
authors.initials: L
authors.lastname: Ma
authors.affiliation: Departments of Pediatrics, Neurology and Physiology, Northwestern University Feinberg School of Medicine, Lurie Children's Hospital of Chicago Research Center, IL 60611, Chicago. Electronic address: ma@northwestern.edu.
authors.forename: Yong-Chao
authors.initials: YC
authors.lastname: Ma
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology*; D009134:Muscular Atrophy, Spinal / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C526471:SMN1 protein, human; C526472:Smn1 protein, mouse; C526473:Smn1 protein, rat; D055533:Survival of Motor Neuron 1 Protein
keywords: Animal disease models; C. elegans; Drosophila; SMA; SMN; Zebrafish
references.citation: Ann Neurol. 2013 Aug;74(2):180-7
references.pmid: 23720273
references.citation: Nat Rev Neurosci. 2009 Aug;10(8):597-609
references.pmid: 19584893
references.citation: J Cell Biol. 2011 Feb 7;192(3):481-95
references.pmid: 21300852
references.citation: Eur J Hum Genet. 2004 Jan;12(1):59-65
references.pmid: 14560316
references.citation: Hum Mol Genet. 2005 Mar 15;14(6):845-57
references.pmid: 15703193
references.citation: Hum Mol Genet. 2003 Oct 1;12(19):2481-9
references.pmid: 12915451
references.citation: RNA. 2013 Nov;19(11):1510-6
references.pmid: 24006466
references.citation: Nat Genet. 2003 Aug;34(4):460-3
references.pmid: 12833158
references.citation: J Neuropathol Exp Neurol. 2009 May;68(5):474-81
references.pmid: 19525895
references.citation: J Cell Biol. 2003 Nov 24;163(4):801-12
references.pmid: 14623865
references.citation: Am J Hum Genet. 2006 Jan;78(1):63-77
references.pmid: 16385450
references.citation: Nat Biotechnol. 2013 Mar;31(3):227-9
references.pmid: 23360964
references.citation: Nat Biotechnol. 2011 Aug 05;29(8):699-700
references.pmid: 21822242
references.citation: J Neurol Sci. 1975 Nov;26(3):349-59
references.pmid: 127019
references.citation: J Neurosci. 2012 Jun 20;32(25):8703-15
references.pmid: 22723710
references.citation: Nature. 2009 Jan 15;457(7227):277-80
references.pmid: 19098894
references.citation: PLoS One. 2007 Sep 26;2(9):e921
references.pmid: 17895963
references.citation: Neurochem Int. 2004 Dec;45(7):1107-12
references.pmid: 15337310
references.citation: J Clin Invest. 2007 Mar;117(3):659-71
references.pmid: 17318264
references.citation: Hum Mol Genet. 2009 Oct 1;18(19):3615-25
references.pmid: 19592581
references.citation: Cell. 2008 May 16;133(4):585-600
references.pmid: 18485868
references.citation: Ann Neurol. 2003 Nov;54(5):647-54
references.pmid: 14595654
references.citation: Dis Model Mech. 2010 Sep-Oct;3(9-10):652-62
references.pmid: 20504969
references.citation: Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9920-5
references.pmid: 9275227
references.citation: Ann N Y Acad Sci. 2006 Nov;1086:21-34
references.pmid: 17185503
references.citation: Neuromuscul Disord. 1992;2(5-6):423-8
references.pmid: 1300191
references.citation: PLoS Genet. 2011 Apr;7(4):e1002030
references.pmid: 21490958
references.citation: Nat Genet. 2002 Apr;30(4):377-84
references.pmid: 11925564
references.citation: Dev Biol. 2009 Aug 1;332(1):142-55
references.pmid: 19464282
references.citation: Lancet. 2008 Jun 21;371(9630):2120-33
references.pmid: 18572081
references.citation: Cell. 2012 Oct 12;151(2):427-39
references.pmid: 23063130
references.citation: Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19348-53
references.pmid: 24191055
references.citation: Hum Mol Genet. 2008 Aug 15;17(16):2552-69
references.pmid: 18492800
references.citation: EMBO J. 2010 Jun 2;29(11):1817-29
references.pmid: 20400941
references.citation: Nat Cell Biol. 2001 Nov;3(11):945-9
references.pmid: 11715014
references.citation: Cell. 1995 Jan 13;80(1):155-65
references.pmid: 7813012
references.citation: Biochem Biophys Res Commun. 2010 Jan 1;391(1):517-22
references.pmid: 19961830
references.citation: PLoS Genet. 2009 Dec;5(12):e1000773
references.pmid: 20019802
references.citation: Neuropathology. 2009 Feb;29(1):63-7
references.pmid: 18410269
references.citation: Hum Mol Genet. 2003 Jun 15;12(12):1367-76
references.pmid: 12783845
references.citation: Annu Rev Neurosci. 2004;27:723-49
references.pmid: 15217349
references.citation: Nat Rev Genet. 2002 Sep;3(9):717-24
references.pmid: 12209146
references.citation: Hum Mol Genet. 2009 Jan 1;18(1):97-104
references.pmid: 18829666
references.citation: Proc Natl Acad Sci U S A. 2013 Jun 25;110(26):E2371-80
references.pmid: 23757500
references.citation: Muscle Nerve. 2010 Jul;42(1):144-7
references.pmid: 20583119
references.citation: Trends Mol Med. 2013 Jan;19(1):40-50
references.pmid: 23228902
references.citation: Nature. 2007 Mar 1;446(7131):71-5
references.pmid: 17330042
references.citation: Hum Mol Genet. 2000 Feb 12;9(3):333-9
references.pmid: 10655541
references.citation: Hum Mol Genet. 1999 Nov;8(12):2133-43
references.pmid: 10545592
references.citation: Curr Neurol Neurosci Rep. 2010 Mar;10(2):108-17
references.pmid: 20425235
references.citation: J Cell Biol. 2003 Jan 6;160(1):41-52
references.pmid: 12515823
references.citation: Hum Mol Genet. 2005 May 1;14(9):1199-210
references.pmid: 15790598
references.citation: J Neurosci. 2013 Jan 30;33(5):2177-87
references.pmid: 23365253
references.citation: Hum Mol Genet. 1995 Oct;4(10):1927-33
references.pmid: 8595417
references.citation: PLoS One. 2008 Sep 15;3(9):e3209
references.pmid: 18791638
references.citation: Ann Neurol. 2010 Jun;67(6):739-48
references.pmid: 20517935
references.citation: Cell. 2012 Oct 12;151(2):440-54
references.pmid: 23063131
references.citation: Mol Neurodegener. 2011 Mar 28;6(1):24
references.pmid: 21443782
references.citation: Science. 2002 Nov 29;298(5599):1775-9
references.pmid: 12459587
references.citation: Curr Opin Neurobiol. 2011 Feb;21(1):110-5
references.pmid: 20970321
references.citation: Neuron. 2011 Feb 10;69(3):453-67
references.pmid: 21315257
references.citation: FEBS Lett. 2000 Dec 8;486(2):99-102
references.pmid: 11113446
references.citation: PLoS One. 2012;7(4):e35462
references.pmid: 22558154
references.citation: J Cell Biol. 2007 Mar 12;176(6):831-41
references.pmid: 17353360
references.citation: J Biol Chem. 2004 Apr 9;279(15):14803-11
references.pmid: 14742439
references.citation: Lancet. 1980 Apr 26;1(8174):919-22
references.pmid: 6103267
references.citation: Mol Biol Cell. 2009 Jan;20(1):90-101
references.pmid: 18923150
references.citation: Brain Res. 2012 Dec 13;1489:66-80
references.pmid: 23103409
references.citation: J Med Genet. 2008 Oct;45(10):635-8
references.pmid: 18662980
references.citation: Nature. 2011 Oct 05;478(7367):123-6
references.pmid: 21979052
references.citation: PLoS One. 2013;8(4):e60113
references.pmid: 23565191
references.citation: PLoS One. 2010 Nov 11;5(11):e15457
references.pmid: 21085654
references.citation: Neuron. 2005 Dec 22;48(6):885-96
references.pmid: 16364894
references.citation: Genomics. 1996 Mar 15;32(3):479-82
references.pmid: 8838816
references.citation: J Cell Biol. 2003 Sep 1;162(5):919-31
references.pmid: 12952942
references.citation: PLoS One. 2010 Aug 19;5(8):e12140
references.pmid: 20808854
references.citation: Neurology. 2003 Mar 25;60(6):983-7
references.pmid: 12654964
references.citation: Nat Genet. 2000 Jan;24(1):66-70
references.pmid: 10615130
references.citation: Nat Biotechnol. 2010 Mar;28(3):271-4
references.pmid: 20190738
references.citation: Hum Mol Genet. 1999 May;8(5):775-82
references.pmid: 10196366
references.citation: PLoS Genet. 2008 Nov;4(11):e1000265
references.pmid: 19023405
references.citation: Hum Mutat. 2000;15(3):228-37
references.pmid: 10679938
references.citation: Cell. 1998 Nov 25;95(5):615-24
references.pmid: 9845364
references.citation: Ann Neurol. 2005 May;57(5):704-12
references.pmid: 15852397
references.citation: J Neurosci. 2013 Apr 10;33(15):6557-62
references.pmid: 23575853
references.citation: Pediatr Neurol. 2012 Jan;46(1):1-12
references.pmid: 22196485
references.citation: Hum Mol Genet. 2011 Jan 15;20(2):245-60
references.pmid: 20962036
references.citation: Cell Rep. 2012 Jun 28;1(6):624-31
references.pmid: 22813737
references.citation: Hum Mol Genet. 2011 Feb 15;20(4):641-8
references.pmid: 21098506
references.citation: Am J Med Genet. 2002 Jul 15;110(4):301-7
references.pmid: 12116201
references.citation: J Cell Biol. 2001 Mar 5;152(5):1107-14
references.pmid: 11238465
references.citation: Chem Biol. 2004 Nov;11(11):1489-93
references.pmid: 15555999
references.citation: Proc Natl Acad Sci U S A. 2011 Jun 21;108(25):10337-42
references.pmid: 21652774
references.citation: Neurology. 2012 Nov 13;79(20):2050-5
references.pmid: 23115209
references.citation: Hum Mol Genet. 2012 Jan 1;21(1):185-95
references.pmid: 21968514
references.citation: Neurology. 2006 Apr 11;66(7):1067-73
references.pmid: 16481599
references.citation: Hum Mol Genet. 2000 Mar 22;9(5):849-58
references.pmid: 10749994
references.citation: PLoS Genet. 2010 Oct 28;6(10):e1001172
references.pmid: 21124729
references.citation: Acta Neuropathol. 2003 Nov;106(5):441-8
references.pmid: 12898156
references.citation: Hum Genet. 2006 Nov;120(4):589-601
references.pmid: 16951947