SMN2

Summary

Gene Symbol: SMN2
Description: survival of motor neuron 2, centromeric
Alias: BCD541, C-BCD541, GEMIN1, SMNC, TDRD16B, survival motor neuron protein, component of gems 1, gemin-1, tudor domain containing 16B
Species: human

Top Publications

  1. pmc Splicing of a critical exon of human Survival Motor Neuron is regulated by a unique silencer element located in the last intron
    Nirmal K Singh
    Department of Medicine LRB 326, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA
    Mol Cell Biol 26:1333-46. 2006
  2. ncbi An 11 base pair duplication in exon 6 of the SMN gene produces a type I spinal muscular atrophy (SMA) phenotype: further evidence for SMN as the primary SMA-determining gene
    D W Parsons
    Department of Pathology, College of Biological Sciences, Ohio State University College of Medicine, Columbus 43210, USA
    Hum Mol Genet 5:1727-32. 1996
  3. ncbi Disruption of an SF2/ASF-dependent exonic splicing enhancer in SMN2 causes spinal muscular atrophy in the absence of SMN1
    Luca Cartegni
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
    Nat Genet 30:377-84. 2002
  4. ncbi The SMN complex, an assemblyosome of ribonucleoproteins
    Sergey Paushkin
    Howard Hughes Medical Institute, and the Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6148, USA
    Curr Opin Cell Biol 14:305-12. 2002
  5. ncbi Genetic testing and risk assessment for spinal muscular atrophy (SMA)
    Shuji Ogino
    Department of Pathology, Brigham and Women s Hospital, Boston, MA 02115, USA
    Hum Genet 111:477-500. 2002
  6. ncbi Identification and characterization of a spinal muscular atrophy-determining gene
    S Lefebvre
    Unite de Recherches sur les Handicaps Genetiques de l Enfant, Institut National de la Sante et de la Recherche Medicale, Institut Necker, Hopital des Enfants Malades, Paris, France
    Cell 80:155-65. 1995
  7. ncbi SMN mRNA and protein levels in peripheral blood: biomarkers for SMA clinical trials
    C J Sumner
    Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA
    Neurology 66:1067-73. 2006
  8. ncbi Sequence of a 131-kb region of 5q13.1 containing the spinal muscular atrophy candidate genes SMN and NAIP
    Q Chen
    Solange Gauthier Karsh Laboratory, Children s Hospital of Eastern Ontario, Ottawa, Canada
    Genomics 48:121-7. 1998
  9. ncbi Characterization of two evolutionarily conserved, alternatively spliced nuclear phosphoproteins, NFAR-1 and -2, that function in mRNA processing and interact with the double-stranded RNA-dependent protein kinase, PKR
    L R Saunders
    Department of Microbiology and Immunology and Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida 33136, USA
    J Biol Chem 276:32300-12. 2001
  10. ncbi Survival motor neuron gene transcript analysis in muscles from spinal muscular atrophy patients
    M Gennarelli
    Dipartimento di Sanita Pubblica e Biologia Cellulare, Universita Tor Vergata, Roma, Italy
    Biochem Biophys Res Commun 213:342-8. 1995

Research Grants

  1. Judith A Steen; Fiscal Year: 2014
  2. Small Oligonucleotides As Therapeutic Agents Of Spinal Muscular Atrophy
    Ravindra N Singh; Fiscal Year: 2012
  3. High-affinity RNA targets of Survival Motor Neuron Protein
    Ravindra N Singh; Fiscal Year: 2013
  4. Arthur H M Burghes; Fiscal Year: 2014
  5. Testing Compounds that Increase SMN levels for Efficacy in Mouse Models of SMA
    Elliot J Androphy; Fiscal Year: 2010
  6. Motor neuron generation from SMA patient-derived induced pluripotent stem cells
    Allison D Ebert; Fiscal Year: 2010
  7. Motoneuron-selective Rescue of SMA Model Mice
    Mendell Rimer; Fiscal Year: 2012
  8. Tetracycline derivatives as SMN2 mRNA splicing modifiers for treatment of SMA.
    S Ken Tanaka; Fiscal Year: 2013
  9. Cooperative lead development program for treatment of spinal muscular atrophy
    Elliot J Androphy; Fiscal Year: 2012
  10. Michelle L Hastings; Fiscal Year: 2014

Detail Information

Publications182 found, 100 shown here

  1. pmc Splicing of a critical exon of human Survival Motor Neuron is regulated by a unique silencer element located in the last intron
    Nirmal K Singh
    Department of Medicine LRB 326, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA
    Mol Cell Biol 26:1333-46. 2006
    Humans have two nearly identical copies of the Survival Motor Neuron (SMN) gene, SMN1 and SMN2. In spinal muscular atrophy (SMA), SMN2 is not able to compensate for the loss of SMN1 due to exclusion of exon 7...
  2. ncbi An 11 base pair duplication in exon 6 of the SMN gene produces a type I spinal muscular atrophy (SMA) phenotype: further evidence for SMN as the primary SMA-determining gene
    D W Parsons
    Department of Pathology, College of Biological Sciences, Ohio State University College of Medicine, Columbus 43210, USA
    Hum Mol Genet 5:1727-32. 1996
    ..One of these, the survival motor neuron (SMN) cDNA, is encoded by two genes (SMNT and SMNC) which are distinguished by base changes in exons 7 and 8...
  3. ncbi Disruption of an SF2/ASF-dependent exonic splicing enhancer in SMN2 causes spinal muscular atrophy in the absence of SMN1
    Luca Cartegni
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
    Nat Genet 30:377-84. 2002
    ..survival of motor neuron 1 gene (SMN1), even though all affected individuals carry a nearly identical, normal SMN2 gene...
  4. ncbi The SMN complex, an assemblyosome of ribonucleoproteins
    Sergey Paushkin
    Howard Hughes Medical Institute, and the Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6148, USA
    Curr Opin Cell Biol 14:305-12. 2002
    ..This forms symmetrical dimethylarginines within the RG-rich domains of the substrates, thereby converting them to high-affinity binders of the SMN complex, and most likely providing regulation of the ribonucleoprotein assembly processes...
  5. ncbi Genetic testing and risk assessment for spinal muscular atrophy (SMA)
    Shuji Ogino
    Department of Pathology, Brigham and Women s Hospital, Boston, MA 02115, USA
    Hum Genet 111:477-500. 2002
    ..SMN gene dosage analyses, which can determine the copy numbers of SMN1 and SMN2 (an SMN1 homolog and a modifier for SMA), have been developed for SMA carrier testing and to confirm that SMN1 is ..
  6. ncbi Identification and characterization of a spinal muscular atrophy-determining gene
    S Lefebvre
    Unite de Recherches sur les Handicaps Genetiques de l Enfant, Institut National de la Sante et de la Recherche Medicale, Institut Necker, Hopital des Enfants Malades, Paris, France
    Cell 80:155-65. 1995
    ..These data suggest that this gene, termed the survival motor neuron (SMN) gene, is an SMA-determining gene...
  7. ncbi SMN mRNA and protein levels in peripheral blood: biomarkers for SMA clinical trials
    C J Sumner
    Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA
    Neurology 66:1067-73. 2006
    ..Clinical trials of drugs that increase SMN protein levels in vitro are currently under way in patients with spinal muscular atrophy...
  8. ncbi Sequence of a 131-kb region of 5q13.1 containing the spinal muscular atrophy candidate genes SMN and NAIP
    Q Chen
    Solange Gauthier Karsh Laboratory, Children s Hospital of Eastern Ontario, Ottawa, Canada
    Genomics 48:121-7. 1998
    ..The Alu-rich NAIP-SMNtel interval contains the microsatellite polymorphisms that are deleted in as many as 80% of type I SMA chromosomes, focusing attention on this region in the pathogenesis of type I SMA...
  9. ncbi Characterization of two evolutionarily conserved, alternatively spliced nuclear phosphoproteins, NFAR-1 and -2, that function in mRNA processing and interact with the double-stranded RNA-dependent protein kinase, PKR
    L R Saunders
    Department of Microbiology and Immunology and Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida 33136, USA
    J Biol Chem 276:32300-12. 2001
    ..Collectively, our data indicate that the NFARs may facilitate double-stranded RNA-regulated gene expression at the level of post-transcription and possibly contribute to host defense-related mechanisms in the cell...
  10. ncbi Survival motor neuron gene transcript analysis in muscles from spinal muscular atrophy patients
    M Gennarelli
    Dipartimento di Sanita Pubblica e Biologia Cellulare, Universita Tor Vergata, Roma, Italy
    Biochem Biophys Res Commun 213:342-8. 1995
    ..Our results suggest that multiple RNA splicing is operative in the two SMN-related genes and that SMN-related polypeptides may be active in the muscle...
  11. ncbi Missense mutation clustering in the survival motor neuron gene: a role for a conserved tyrosine and glycine rich region of the protein in RNA metabolism?
    K Talbot
    University of Oxford, Department of Biochemistry, UK
    Hum Mol Genet 6:497-500. 1997
    ..We have identified apparent orthologues of SMN in Caenorhabditis elegans and Schizosaccharomyces pombe. These sequences retain the highly conserved Y-G motif and provide additional support for a role of SMN in mRNA metabolism...
  12. ncbi The survival motor neuron protein in spinal muscular atrophy
    D D Coovert
    Department of Molecular Genetics, College of Biological Sciences, Ohio State University, Columbus 43210, USA
    Hum Mol Genet 6:1205-14. 1997
    ..We suggest that disruption of SMN(T) in type I patients results in loss of SMN from motor neurons, resulting in the degeneration of these neurons...
  13. ncbi The spinal muscular atrophy disease gene product, SMN, and its associated protein SIP1 are in a complex with spliceosomal snRNP proteins
    Q Liu
    Howard Hughes Medical Institute, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia 19104 6148, USA
    Cell 90:1013-21. 1997
    ..These findings suggest a role for SMN and SIP1 in spliceosomal snRNP biogenesis and function and provide a likely molecular mechanism for the cause of SMA...
  14. pmc Intragenic telSMN mutations: frequency, distribution, evidence of a founder effect, and modification of the spinal muscular atrophy phenotype by cenSMN copy number
    D W Parsons
    Department of Pathology, Ohio State University, Columbus, Ohio, USA
    Am J Hum Genet 63:1712-23. 1998
    ..We note that telSMN missense mutations are associated with milder disease in our patients and that the severe type I SMA phenotype caused by frameshift mutations can be ameliorated by an increase in cenSMN gene copy number...
  15. ncbi A novel function for SMN, the spinal muscular atrophy disease gene product, in pre-mRNA splicing
    L Pellizzoni
    Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia 19104 6148, USA
    Cell 95:615-24. 1998
    ..These findings demonstrate that SMN plays a crucial role in the generation of the pre-mRNA splicing machinery and thus in mRNA biogenesis, and they link the function of SMN in this pathway to SMA...
  16. ncbi A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2
    U R Monani
    Department of Neurology, The Ohio State University, Columbus 43210, USA
    Hum Mol Genet 8:1177-83. 1999
    ..Alterations within an almost identical copy gene, the centromeric survival motor neuron 2 ( SMN2 ) gene produce no known phenotypic effect...
  17. ncbi Essential role for the tudor domain of SMN in spliceosomal U snRNP assembly: implications for spinal muscular atrophy
    D Buhler
    Max Planck Institut fur Biochemie, Am Klopferspitz 18a, D 82152 Martinsried, Germany
    Hum Mol Genet 8:2351-7. 1999
    ..Thus, our data show that SMN is an essential U snRNP assembly factor and establish a direct correlation between defects in the biogenesis of U snRNPs and SMA...
  18. pmc Gemin3: A novel DEAD box protein that interacts with SMN, the spinal muscular atrophy gene product, and is a component of gems
    B Charroux
    Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6148, USA
    J Cell Biol 147:1181-94. 1999
    ..The presence of a DEAD box motif in Gemin3 suggests that it may provide the catalytic activity that plays a critical role in the function of the SMN complex on RNPs...
  19. ncbi SMN tudor domain structure and its interaction with the Sm proteins
    P Selenko
    Structural and Computational Biology, EMBL, Meyerhofstr 1, D 69012 Heidelberg, Germany
    Nat Struct Biol 8:27-31. 2001
    ..Our data provide a structural basis for a molecular defect underlying SMA...
  20. ncbi Spinal muscular atrophy disrupts the interaction of ZPR1 with the SMN protein
    L Gangwani
    Program in Molecular Medicine, University of Massachussetts Medical School, 373 Plantation St, Worcester, Massachussetts 01605, USA
    Nat Cell Biol 3:376-83. 2001
    ..Similarly, decreased ZPR1 expression prevents SMN localization to nuclear bodies. Our data show that ZPR1 is required for the localization of SMN in nuclear bodies...
  21. pmc SMN interacts with a novel family of hnRNP and spliceosomal proteins
    Z Mourelatos
    Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6148, USA
    EMBO J 20:5443-52. 2001
    ..We further demonstrate that hnRNP Qs are required for efficient pre-mRNA splicing in vitro. The hnRNP Q proteins may provide a molecular link between the SMN complex and splicing...
  22. ncbi Gemin5, a novel WD repeat protein component of the SMN complex that binds Sm proteins
    Amelie K Gubitz
    Howard Hughes Medical Institute, Department of Biochemistry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6148, USA
    J Biol Chem 277:5631-6. 2002
    ..The presence of 13 WD repeat domains in the amino-terminal half of Gemin5 and a coiled-coil motif near its carboxyl terminus indicate that it may form a large heteromeric complex and engage in multiple interactions...
  23. ncbi Purification of native survival of motor neurons complexes and identification of Gemin6 as a novel component
    Livio Pellizzoni
    Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6148, USA
    J Biol Chem 277:7540-5. 2002
    ..Co-immunoprecipitation, immunolocalization, and in vitro binding experiments demonstrate that Gemin6 is a component of the SMN complex that localizes to gems and interacts with several Sm proteins of the spliceosomal snRNPs...
  24. ncbi Specific interaction of Smn, the spinal muscular atrophy determining gene product, with hnRNP-R and gry-rbp/hnRNP-Q: a role for Smn in RNA processing in motor axons?
    Wilfried Rossoll
    Institut für Klinische Neurobiologie, Department of Neurology, University of Wurzburg, Josef Schneider Strasse 11, D 97080 Wurzburg, Germany
    Hum Mol Genet 11:93-105. 2002
    ..The human genome, in contrast to mouse, contains a second SMN gene (SMN2) which codes for a gene product which is alternatively spliced at the C-terminus, but also gives rise to low levels ..
  25. pmc Quantitative analyses of SMN1 and SMN2 based on real-time lightCycler PCR: fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy
    Markus Feldkötter
    Institute of Human Genetics, University Clinic, Rheinische Friedrich Wilhelms University Bonn, Bonn, Germany
    Am J Hum Genet 70:358-68. 2002
    ..b>SMN2, a copy gene, influences the severity of SMA and may be used in somatic gene therapy of patients with SMA in the ..
  26. doi Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2
    Matthew D Mailman
    Department of Pathology, The Ohio State University, Columbus 43210, USA
    Genet Med 4:20-6. 2002
    This study describes SMN1 deletion frequency, carrier studies, and the effect of the modifying SMN2 gene on the spinal muscular atrophy (SMA) phenotype...
  27. ncbi SRp30c-dependent stimulation of survival motor neuron (SMN) exon 7 inclusion is facilitated by a direct interaction with hTra2 beta 1
    Philip J Young
    Arizona State University, Department of Biology, Tempe, AZ 85287 1501, USA
    Hum Mol Genet 11:577-87. 2002
    Proximal spinal muscular atrophy (SMA) is caused by the homozygous loss of survival motor neuron (SMN1). SMN2, a nearly identical copy gene, is present in all SMA patients; however this gene cannot provide protection from disease due to ..
  28. ncbi Homozygous exon 7 deletion of the SMN centromeric gene (SMN2): a potential susceptibility factor for adult-onset lower motor neuron disease
    Andoni Echaniz-Laguna
    Service des Maladies du Système Nerveux et du Muscle, Clinique Neurologique, Hĵpital Civil de Strasbourg, France
    J Neurol 249:290-3. 2002
    ..In contrast, the role of the centromeric copy of the SMN gene (SMN2) in MND remains unclear...
  29. ncbi Identification and characterization of Gemin7, a novel component of the survival of motor neuron complex
    Jennifer Baccon
    Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6148, USA
    J Biol Chem 277:31957-62. 2002
    ..With the identification of Gemin7, the inventory of the core components of the SMN complex appears essentially complete...
  30. ncbi A negative element in SMN2 exon 7 inhibits splicing in spinal muscular atrophy
    Tsuyoshi Kashima
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Nat Genet 34:460-3. 2003
    ..Humans possess a linked, nearly identical gene, SMN2, which produces a functional SMN protein but at levels insufficient to compensate for loss of SMN1 (refs. 1,2)...
  31. ncbi Valproic acid increases the SMN2 protein level: a well-known drug as a potential therapy for spinal muscular atrophy
    L Brichta
    Institute of Human Genetics, University of Bonn, Wilhelmstrasse 31, 53111 Bonn, Germany
    Hum Mol Genet 12:2481-9. 2003
    ..motor neuron gene (SMN1) is the primary cause of SMA, while SMA severity is mainly determined by the number of SMN2 copies...
  32. ncbi Survival motor neuron SMN1 and SMN2 gene promoters: identical sequences and differential expression in neurons and non-neuronal cells
    Bernadett Boda
    Neurogénétique INSERM E9935, Hopital Robert Debre, 48 Boulevard Serurier, Paris, France
    Eur J Hum Genet 12:729-37. 2004
    ..of motor neuron 1 gene (SMN1) is the main cause of SMA, but disease severity depends primarily on the number of SMN2 gene copies...
  33. ncbi Molecular and functional analysis of intragenic SMN1 mutations in patients with spinal muscular atrophy
    Y Sun
    Institute of Human Genetics, University of Cologne, Cologne, Germany
    Hum Mutat 25:64-71. 2005
    ..The severity of the disease is mainly determined by the copy number of SMN2, a copy gene which predominantly produces exon 7-skipped transcripts and only low amount of full-length transcripts ..
  34. ncbi A non-sequence-specific requirement for SMN protein activity: the role of aminoglycosides in inducing elevated SMN protein levels
    Elizabeth C Wolstencroft
    Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211 7310, USA
    Hum Mol Genet 14:1199-210. 2005
    ..In virtually all SMA patients, a nearly identical copy gene is present, SMN2. SMN2 cannot fully compensate for the loss of SMN1 because the majority of transcripts derived from SMN2 lack a ..
  35. ncbi SMN genotypes producing less SMN protein increase susceptibility to and severity of sporadic ALS
    J H Veldink
    Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center, Utrecht, The Netherlands
    Neurology 65:820-5. 2005
    ..in two highly homologous variants: SMN1, the causative gene responsible for the production of the majority of functional SMN protein, and SMN2, responsible for the production of less protein but sufficient for modifying the SMA phenotype.
  36. ncbi SMN1 gene, but not SMN2, is a risk factor for sporadic ALS
    P Corcia
    INSERM U619, Faculte de Medecine, Tours, France
    Neurology 67:1147-50. 2006
    SMN1 gene deletions cause spinal muscular atrophy, and SMN2 gene deletions have been associated with sporadic lower motor neuron diseases.
  37. pmc An intronic element contributes to splicing repression in spinal muscular atrophy
    Tsuyoshi Kashima
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    Proc Natl Acad Sci U S A 104:3426-31. 2007
    ..b>SMN2 is a nearly identical copy of SMN1 that is unable to prevent disease, because most SMN2 transcripts lack exon 7 and ..
  38. ncbi hnRNP A1 functions with specificity in repression of SMN2 exon 7 splicing
    Tsuyoshi Kashima
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    Hum Mol Genet 16:3149-59. 2007
    ..SMN1 has been duplicated in humans to create SMN2, which produces a low level of functional SMN protein...
  39. ncbi 5-(N-ethyl-N-isopropyl)-amiloride enhances SMN2 exon 7 inclusion and protein expression in spinal muscular atrophy cells
    Chung Yee Yuo
    Faculty of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China
    Ann Neurol 63:26-34. 2008
    ..All SMA patients carry at least one copy of a nearly identical SMN2 gene...
  40. doi Congenital heart disease is a feature of severe infantile spinal muscular atrophy
    S Rudnik-Schoneborn
    Institute of Human Genetics, Technical University of Aachen, Pauwelsstr 30, D 52074 Aachen, Germany
    J Med Genet 45:635-8. 2008
    ..The presence of at least one SMN2 gene copy is required for normal embryogenesis...
  41. pmc TDP-43 overexpression enhances exon 7 inclusion during the survival of motor neuron pre-mRNA splicing
    Jayarama Krishnan Bose
    Institute of Molecular Medicine, National Taiwan University, Taipei 106, Taiwan
    J Biol Chem 283:28852-9. 2008
    ..Furthermore, both RNA-recognition motif domains are required for its ability to enhance the SMN2 exon 7 inclusion...
  42. pmc Survival motor neuron gene 2 silencing by DNA methylation correlates with spinal muscular atrophy disease severity and can be bypassed by histone deacetylase inhibition
    Jan Hauke
    Institute of Human Genetics, University ofCologne, Cologne, Germany
    Hum Mol Genet 18:304-17. 2009
    ..of the survival motor neuron gene 1 (SMN1), while the disease severity is mainly influenced by the number of SMN2 gene copies...
  43. doi An assembly chaperone collaborates with the SMN complex to generate spliceosomal SnRNPs
    Ashwin Chari
    Department of Biochemistry, Biocenter, University of Wurzburg, Am Hubland, D 97074 Wurzburg, Germany
    Cell 135:497-509. 2008
    ..The mode of action of this combined chaperone/catalyst system is reminiscent of the mechanism employed by DNA clamp loaders...
  44. pmc Differential 3' splice site recognition of SMN1 and SMN2 transcripts by U2AF and U2 snRNP
    Mafalda Martins de Araujo
    Centre de Regulacio Genomica, Barcelona, Spain
    RNA 15:515-23. 2009
    ..A paralog of the gene, SMN2, cannot provide adequate levels of functional SMN because exon 7 is skipped in a significant fraction of the mature ..
  45. pmc A SMN missense mutation complements SMN2 restoring snRNPs and rescuing SMA mice
    Eileen Workman
    Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH 43210, USA
    Hum Mol Genet 18:2215-29. 2009
    ..Loss of the survival motor neuron (SMN1) gene, in the presence of the SMN2 gene causes SMA...
  46. pmc SMN transcript levels in leukocytes of SMA patients determined by absolute real-time PCR
    Francesco Danilo Tiziano
    Institute of Medical Genetics, Catholic University, Largo Francesco Vito, 1, 00168 Rome, Italy
    Eur J Hum Genet 18:52-8. 2010
    ..All patients have at least one or more (usually 2-4) copies of a highly homologous gene (SMN2), which produces insufficient levels of functional SMN protein, because of alternative splicing of exon 7...
  47. ncbi HnRNP C1/C2 may regulate exon 7 splicing in the spinal muscular atrophy gene SMN1
    Sanae Irimura
    Department of Genetic Epidemiology, Kobe University Graduate School of Medicine, Kobe, Japan
    Kobe J Med Sci 54:E227-36. 2009
    Spinal muscular atrophy (SMA) is caused by loss of SMN1. A nearly identical gene, SMN2, fails to compensate for the loss of SMN1 because SMN2 produces mainly an exon 7-skipped product...
  48. doi p38 Mitogen-activated protein kinase stabilizes SMN mRNA through RNA binding protein HuR
    Faraz Farooq
    University of Ottawa, Ottawa K1H 8M5, Canada
    Hum Mol Genet 18:4035-45. 2009
    ..A potential treatment strategy for SMA is to upregulate levels of SMN protein originating from the SMN2 gene compensating in part for the absence of functional SMN1 gene...
  49. pmc A positive modifier of spinal muscular atrophy in the SMN2 gene
    Thomas W Prior
    Department of Pathology, Ohio State University, Columbus, OH 43210, USA
    Am J Hum Genet 85:408-13. 2009
    ..A nearly identical gene, SMN2, has been shown to decrease the severity of SMA in a dose-dependent manner...
  50. doi An analysis of disease severity based on SMN2 copy number in adults with spinal muscular atrophy
    Bakri Elsheikh
    Department of Neurology, Ohio State University, 421 Means Hall, 1654 Upham Drive, Columbus, Ohio 43210, USA
    Muscle Nerve 40:652-6. 2009
    To evaluate the effect of SMN2 copy number on disease severity in spinal muscular atrophy (SMA), we stratified 45 adult SMA patients based on SMN2 copy number (3 vs. 4 copies)...
  51. pmc The splicing regulator Sam68 binds to a novel exonic splicing silencer and functions in SMN2 alternative splicing in spinal muscular atrophy
    Simona Pedrotti
    Department of Public Health and Cell Biology, University of Rome Tor Vergata, Rome, Italy
    EMBO J 29:1235-47. 2010
    ..An almost identical SMN2 gene is unable to compensate for this deficiency because a single C-to-T transition at position +6 in exon-7 causes ..
  52. pmc Splicing regulation of the survival motor neuron genes and implications for treatment of spinal muscular atrophy
    Thomas W Bebee
    The Molecular, Cellular, and Developmental Biology MCDB Graduate Program, The Ohio State University, Columbus, Ohio, USA
    Front Biosci (Landmark Ed) 15:1191-204. 2010
    ..The reduced SMN levels are due to loss of the survival motor neuron-1 (SMN1) gene. Humans carry a nearly identical SMN2 gene that generates a truncated protein, due to a C to T nucleotide alteration in exon 7 that leads to inefficient ..
  53. pmc Reduced survival of motor neuron (SMN) protein in motor neuronal progenitors functions cell autonomously to cause spinal muscular atrophy in model mice expressing the human centromeric (SMN2) gene
    Gyu Hwan Park
    Department of Neurology, Columbia University Medical Center, New York, New York 10032, USA
    J Neurosci 30:12005-19. 2010
    ..This realization is tempered by the relatively mild SMA phenotype in our model mice, one explanation for which is the presence of normal SMN levels in non-neuronal tissue that serves to modulate disease severity...
  54. pmc A feedback loop regulates splicing of the spinal muscular atrophy-modifying gene, SMN2
    Francine M Jodelka
    Department of Cell Biology and Anatomy, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA
    Hum Mol Genet 19:4906-17. 2010
    ..SMN protein is also encoded by SMN2. However, splicing of SMN2 exon 7 is defective, and consequently, the majority of the transcripts produce a ..
  55. ncbi Association between survivor motor neuron 2 (SMN2) gene homozygous deletion and sporadic lower motor neuron disease in a Korean population
    Juwon Kim
    Dept of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea
    Ann Clin Lab Sci 40:368-74. 2010
    ..We genotyped the copy number of SMN1 and SMN2 in 18 patients diagnosed with sporadic LMND and 100 neurologically healthy subjects using the multiplex ligation-..
  56. doi SMN2 exon 7 splicing is inhibited by binding of hnRNP A1 to a common ESS motif that spans the 3' splice site
    Thomas Koed Doktor
    Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark
    Hum Mutat 32:220-30. 2011
    Spinal Muscular Atrophy is caused by homozygous loss of SMN1 with phenotypic modulation by SMN2. SMN2 expresses only limited amounts of full-length transcript due to skipping of exon 7 caused by disruption of an SF2/ASF binding ESE...
  57. pmc TIA1 prevents skipping of a critical exon associated with spinal muscular atrophy
    Natalia N Singh
    Department of Biomedical Sciences, College of Veterinary Medicine, 2034 Veterinary Medicine Bldg, Iowa State University, Ames, IA 50011, USA
    Mol Cell Biol 31:935-54. 2011
    Prevention of skipping of exon 7 during pre-mRNA splicing of Survival Motor Neuron 2 (SMN2) holds the promise for cure of spinal muscular atrophy (SMA), a leading genetic cause of infant mortality...
  58. pmc Structure of a key intermediate of the SMN complex reveals Gemin2's crucial function in snRNP assembly
    Rundong Zhang
    Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6148, USA
    Cell 146:384-95. 2011
    ..These findings provide insight into SMN complex assembly and specificity, linking snRNP biogenesis and SMA pathogenesis...
  59. pmc Hypoxia is a modifier of SMN2 splicing and disease severity in a severe SMA mouse model
    Thomas W Bebee
    The Center for Childhood Cancer at the Research Institute at Nationwide Children s Hospital, Columbus, OH, USA
    Hum Mol Genet 21:4301-13. 2012
    ..Reduced levels of SMN is due to the loss of the SMN1 gene and inefficient splicing of the SMN2 gene caused by a C>T mutation in exon 7...
  60. pmc The promoters of the survival motor neuron gene (SMN) and its copy (SMNc) share common regulatory elements
    A Echaniz-Laguna
    Institut de Genetique et de Biologie Moleculaire et Cellulaire, Institut National de la Sante et de la Recherche Medicale, CNRS, Universite Louis Pasteur, Strasbourg, France
    Am J Hum Genet 64:1365-70. 1999
    ..SMN is duplicated, and the almost identical copy gene (SMNc) remains functional in patients with SMA...
  61. ncbi Specific sequences of the Sm and Sm-like (Lsm) proteins mediate their interaction with the spinal muscular atrophy disease gene product (SMN)
    W J Friesen
    Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6148, USA
    J Biol Chem 275:26370-5. 2000
    ..These findings demonstrate that arginine- and glycine-rich domains are necessary and sufficient for SMN interaction, and they expand further the range of targets of the SMN protein...
  62. ncbi The exon 2b region of the spinal muscular atrophy protein, SMN, is involved in self-association and SIP1 binding
    P J Young
    MRIC Biochemistry Group, North East Wales Institute, Mold Road, Wrexham LL11 2AW, UK
    Hum Mol Genet 9:2869-77. 2000
    ..The presence of two separate self-association sites suggests a novel mechanism by which linear oligomers or closed rings might be formed from SMN monomers...
  63. ncbi An extended inhibitory context causes skipping of exon 7 of SMN2 in spinal muscular atrophy
    Natalia N Singh
    Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605 2324, USA
    Biochem Biophys Res Commun 315:381-8. 2004
    SMN1 and SMN2 represent the two nearly identical copies of the survival of motor neuron gene in humans...
  64. ncbi The role of histone acetylation in SMN gene expression
    Lauren E Kernochan
    Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA
    Hum Mol Genet 14:1171-82. 2005
    Increasing survival motor neuron 2 (SMN2) gene expression may be an effective strategy for the treatment of spinal muscular atrophy (SMA)...
  65. ncbi Evolving concepts on human SMN pre-mRNA splicing
    Ravindra N Singh
    Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, Iowa 50011, USA
    RNA Biol 4:7-10. 2007
    SMN1 and SMN2 represent two nearly identical copies of the survival motor neuron gene in humans...
  66. pmc The RNA binding protein hnRNP Q modulates the utilization of exon 7 in the survival motor neuron 2 (SMN2) gene
    Hung Hsi Chen
    Institute of Biomedical Sciences, Academia Sinica, 128 Academy Road Section 2, Nankang, Taipei 11529, Taiwan
    Mol Cell Biol 28:6929-38. 2008
    ..The human SMN2 gene has a C-to-T transition at position +6 of exon 7 and thus produces exon 7-skipping mRNAs...
  67. ncbi Characterization of a nuclear 20S complex containing the survival of motor neurons (SMN) protein and a specific subset of spliceosomal Sm proteins
    G Meister
    Max Planck Institute of Biochemistry, Martinsried, Germany
    Hum Mol Genet 9:1977-86. 2000
    ..This shows that the SMN-Sm protein interaction is not restricted to the cytoplasm. Our data imply that nuclear SMN affects splicing by modulating the Sm protein composition of U snRNPs...
  68. doi SMN2 and NAIP gene dosages in Vietnamese patients with spinal muscular atrophy
    Van Khanh Tran
    Department of Pediatrics, Graduate School of Medicine, Kobe University, Japan
    Pediatr Int 50:346-51. 2008
    The SMN1 gene is now recognized as a spinal muscular atrophy (SMA)-causing gene, while SMN2 and NAIP have been characterized as a modifying factor of the clinical severity of SMA...
  69. doi Mutation update of spinal muscular atrophy in Spain: molecular characterization of 745 unrelated patients and identification of four novel mutations in the SMN1 gene
    Laura Alias
    Servicio de Genetica, Hospital de la Santa Creu i Sant Pau, Sant Antoni Ma Claret 167, 08025 Barcelona, Spain
    Hum Genet 125:29-39. 2009
    ..008). Absence of the SMN1 gene was detected in 671 patients (90%), and hybrid SMN1-SMN2 genes were observed in 37 cases (5%). Furthermore, we detected 13 small mutations in 28 patients (3...
  70. doi Histone deacetylase inhibition activity and molecular docking of (e )-resveratrol: its therapeutic potential in spinal muscular atrophy
    Didem Dayangac-Erden
    Department of Medical Biology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
    Chem Biol Drug Des 73:355-64. 2009
    ..is caused by mutation of the survival motor neuron gene (SMN1) but all patients retain a nearly identical copy, SMN2. The disease severity correlates inversely with increased SMN2 copy...
  71. doi [Mutation analysis of SMN gene in a patient and his family with spinal muscular atrophy]
    Jian Zeng
    Fuzhou General Hospital, Nanjing Military Region, Fuzhou, Fujian, 350025 People s Republic of China
    Zhonghua Yi Xue Yi Chuan Xue Za Zhi 26:139-43. 2009
    ..To perform mutation analysis and describe the genotype of the SMN gene in a patient with spinal muscular atrophy (SMA) and his family...
  72. pmc A transgene carrying an A2G missense mutation in the SMN gene modulates phenotypic severity in mice with severe (type I) spinal muscular atrophy
    Umrao R Monani
    Department of Neurology, Ohio State University, Columbus, OH 43210, USA
    J Cell Biol 160:41-52. 2003
    ..lack a functional survival of motor neurons (SMN1) gene, but carry one or more copies of the highly homologous SMN2 gene. A homozygous knockout of the single murine Smn gene is embryonic lethal...
  73. ncbi Selective vulnerability of motor neurons and dissociation of pre- and post-synaptic pathology at the neuromuscular junction in mouse models of spinal muscular atrophy
    Lyndsay M Murray
    Centre for Integrative Physiology, University of Edinburgh Medical School, Edinburgh EH8 9XD, UK
    Hum Mol Genet 17:949-62. 2008
    ..Here we have undertaken a detailed morphological investigation of neuromuscular synaptic pathology in the Smn-/-;SMN2 and Smn-/-;SMN2;Delta7 mouse models of SMA...
  74. pmc Delivery of bifunctional RNAs that target an intronic repressor and increase SMN levels in an animal model of spinal muscular atrophy
    Travis D Baughan
    Department of Molecular Microbiology and Immunology, Bond Life Sciences Center, University of Missouri, Columbia, 65211, USA
    Hum Mol Genet 18:1600-11. 2009
    ..A nearly identical copy gene, SMN2, is present in all SMA patients, which produces low levels of functional protein...
  75. pmc Delivery of recombinant follistatin lessens disease severity in a mouse model of spinal muscular atrophy
    Ferrill F Rose
    Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65211, USA
    Hum Mol Genet 18:997-1005. 2009
    ..Current therapeutic research focuses on modulating the expression of a partially functioning copy gene, SMN2, which is retained in SMA patients...
  76. doi Measurement of muscle strength with a handheld dynamometer in patients with chronic spinal muscular atrophy
    Anna Febrer
    Service of Physical Medicine and Rehabilitation, University Hospital Sant Joan de Deu, Barcelona, Spain
    J Rehabil Med 42:228-31. 2010
    ..To measure muscle strength in patients with spinal muscular atrophy using a handheld dynamometer as an objective tool to evaluate the progression of disease and the outcome of therapeutic trials...
  77. ncbi Mildly affected patients with spinal muscular atrophy are partially protected by an increased SMN2 copy number
    B Wirth
    Institute of Human Genetics, University of Cologne, Kerpener Str 34, 50931, Cologne, Germany
    Hum Genet 119:422-8. 2006
    ..The clinical distinction between SMA type I to IV reflects different age of onset and disease severity. SMN2, a nearly identical copy gene of SMN1, produces only 10% of full-length SMN RNA/protein and is an excellent target ..
  78. doi Synthesis and biological evaluation of novel 2,4-diaminoquinazoline derivatives as SMN2 promoter activators for the potential treatment of spinal muscular atrophy
    John Thurmond
    deCODE Chemistry Inc, Woodridge, IL 60517, USA
    J Med Chem 51:449-69. 2008
    ..Adjacent to SMN1 are a variable number of copies of the SMN2 gene...
  79. pmc Trans-splicing-mediated improvement in a severe mouse model of spinal muscular atrophy
    Tristan H Coady
    Department of Veterinary Pathobiology, Bond Life Sciences Center, University of Missouri, Columbia, Missouri 65211, USA
    J Neurosci 30:126-30. 2010
    ..of Survival Motor Neuron-1 (SMN1), however, all patients retain at least one copy of a nearly identical gene called SMN2. While SMN2 and SMN1 are comprised of identical coding sequences, the majority of SMN2 transcripts are ..
  80. pmc Quantitative analysis of survival motor neuron copies: identification of subtle SMN1 mutations in patients with spinal muscular atrophy, genotype-phenotype correlation, and implications for genetic counseling
    B Wirth
    Institute of Human Genetics, Wilhelmstrasse 31, D 53111 Bonn, Germany
    Am J Hum Genet 64:1340-56. 1999
    ..allowed inference of the effect of each mutation on the function of the SMN1 protein and the role of the SMN2 copy number in modulating the SMA phenotype...
  81. ncbi Neonatal spinal muscular atrophy with multiple contractures, bone fractures, respiratory insufficiency and 5q13 deletion
    M A García-Cabezas
    Departamento de Anatomia Patologica, Hospital Universitario La Paz, Pso de la Castellana 261, 28046 Madrid, Spain
    Acta Neuropathol 107:475-8. 2004
    ..analysis of the patient revealed homozygous deletions of survival motor neuron gene 1 (SMN1) and a single copy of SMN2 in region 5q13...
  82. ncbi Detection of spinal muscular atrophy carriers by nested polymerase chain reaction of single sperm cells
    Yuval Yaron
    Prenatal Diagnosis Unit, Genetic Institute, Tel Aviv Sourasky Medical Center, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Israel
    Genet Test 10:18-23. 2006
    ..Restriction enzyme digestion with DraI was used to differentiate between the highly homologous SMN1 and SMN2 genes. Single sperm cells from five known SMA carriers and six noncarriers were analyzed...
  83. ncbi [Prenatal diagnosis of 5 fetuses with high risk of developing spinal muscular atrophy]
    Feng hua Lan
    Center for Molecular Diagnosis of Genetic Diseases, Fuzhou General Hospital of Nanjing Military Command, Fuzhou, Fujian, 350025 P R China
    Zhonghua Yi Xue Yi Chuan Xue Za Zhi 24:373-7. 2007
    ..To perform prenatal diagnosis for 5 pregnant women who had given birth to children with spinal muscular atrophy (SMA)...
  84. ncbi Efficient strategies for preimplantation genetic diagnosis of spinal muscular atrophy
    Anne Girardet
    Laboratoire de Genetique Moleculaire, Universite Montpellier 1, UFR de Medecine, INSERM, U827, CHU Montpellier, Institut Universitaire de Recherche Clinique IURC, Montpellier, France
    Fertil Steril 90:443.e7-12. 2008
    ..To develop and apply efficient multiplex preimplantation genetic diagnosis (PGD) protocols for spinal muscular atrophy (SMA)...
  85. pmc Effects of 2,4-diaminoquinazoline derivatives on SMN expression and phenotype in a mouse model for spinal muscular atrophy
    Matthew E R Butchbach
    Department of Molecular and Cellular Biochemistry, College of Medicine, The Ohio State University, 1645 Neil Avenue, Columbus, OH 43210, USA
    Hum Mol Genet 19:454-67. 2010
    ..In humans, the SMN gene is duplicated; SMA results from the loss of SMN1 but SMN2 remains intact. SMA severity is related to the copy number of SMN2...
  86. pmc Molecular and phenotypic reassessment of an infrequently used mouse model for spinal muscular atrophy
    Rocky G Gogliotti
    Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60614, USA
    Biochem Biophys Res Commun 391:517-22. 2010
    ..SMA) results from loss of the survival motor neuron 1 (SMN1) gene, with retention of its nearly identical homolog, SMN2. There is a direct correlation between disease severity and SMN2 copy number...
  87. doi Ciliary neurotrophic factor-induced sprouting preserves motor function in a mouse model of mild spinal muscular atrophy
    Christian M Simon
    Institute for Clinical Neurobiology, Josef Schneider Str 11, 97080 Wuerzburg, Germany
    Hum Mol Genet 19:973-86. 2010
    ..Depending on the levels of SMN protein produced from a second SMN gene (SMN2), different forms of the disease are distinguished...
  88. pmc Early heart failure in the SMNDelta7 model of spinal muscular atrophy and correction by postnatal scAAV9-SMN delivery
    Adam K Bevan
    Department of Gene Therapy, The Research Institute, Nationwide Children s Hospital, Columbus, OH 43205, USA
    Hum Mol Genet 19:3895-905. 2010
    ..Therefore, we have characterized left ventricular (LV) function of SMA mice (SMN2+/+; SMNΔ7+/+; Smn-/-) and compared it with that of their unaffected littermates at 7 and 14 days of age...
  89. doi Neurodevelopmental consequences of Smn depletion in a mouse model of spinal muscular atrophy
    Hong Liu
    Ottawa Hospital Research Institute and The University of Ottawa Center for Neuromuscular Disease, Ottawa, Ontario, Canada
    J Neurosci Res 88:111-22. 2010
    ..Furthermore, we examined Smn(-/-);SMN2 mice, a model of very severe SMA, for developmental, morphological, and molecular abnormalities...
  90. doi Therapy development in spinal muscular atrophy
    Michael Sendtner
    Institute for Clinical Neurobiology, University of Wuerzburg, Wuerzburg, Germany
    Nat Neurosci 13:795-9. 2010
    ..Previous therapy approaches have focused on upregulation of SMN expression from a second SMN (SMN2) gene that gives rise to low amounts of functional SMN protein...
  91. doi SAHA ameliorates the SMA phenotype in two mouse models for spinal muscular atrophy
    Markus Riessland
    Institute of Human Genetics, University of Cologne, Cologne, Germany
    Hum Mol Genet 19:1492-506. 2010
    ..loss of the survival motor neuron gene 1 (SMN1), whereas disease severity is mainly influenced by the number of SMN2 copies...
  92. ncbi Exclusion of Htra2-beta1, an up-regulator of full-length SMN2 transcript, as a modifying gene for spinal muscular atrophy
    C Helmken
    Institute of Human Genetics, Bonn, Germany
    Hum Genet 107:554-8. 2000
    ..Due to a single nucleotide difference within SMN1 exon 7 that disrupts an exonic splicing enhancer (ESE), SMN2, a nearly identical copy of SMN1, predominantly expresses alternatively spliced transcripts lacking exon 7, whereas ..
  93. pmc In vivo selection reveals combinatorial controls that define a critical exon in the spinal muscular atrophy genes
    Natalia N Singh
    Department of Medicine LRB 326, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605 2324, USA
    RNA 10:1291-305. 2004
    Humans have two near identical copies of the survival of motor neuron (SMN) gene, SMN1 and SMN2. In spinal muscular atrophy (SMA), SMN2 is not able to compensate for the loss of SMN1 due to an inhibitory mutation at position 6 (C6U ..
  94. ncbi SMNDelta7, the major product of the centromeric survival motor neuron (SMN2) gene, extends survival in mice with spinal muscular atrophy and associates with full-length SMN
    Thanh T Le
    Department of Molecular and Cellular Biochemistry, College of Medicine and Public Health, Ohio State University, Columbus, OH 43210, USA
    Hum Mol Genet 14:845-57. 2005
    ..SMN is encoded by two genes, SMN1 and SMN2, which essentially differ by a single nucleotide in exon 7...
  95. ncbi In vitro restoration of functional SMN protein in human trophoblast cells affected by spinal muscular atrophy by small fragment homologous replacement
    Federica Sangiuolo
    Human Genetics Section, Department of Biopathology, Tor Vergata University, 00133 Rome, Italy
    Hum Gene Ther 16:869-80. 2005
    ..of the survival of motor neuron 1 (SMN1) gene, but they retain a "nonfunctional" copy of the duplicate gene (SMN2) in their genome...
  96. ncbi A sensitive assay for measuring SMN mRNA levels in peripheral blood and in muscle samples of patients affected with spinal muscular atrophy
    Myriam Vezain
    Department of Genetics, Rouen University Hospital and INSERM U614, Institute for Biomedical Research, University of Rouen, Rouen, France
    Eur J Hum Genet 15:1054-62. 2007
    ..in spinal muscular atrophy (SMA) that are aimed at increasing full-length (FL) mRNA levels produced from the SMN2 gene. Assays measuring SMN mRNA levels are needed...
  97. pmc Neuronal SMN expression corrects spinal muscular atrophy in severe SMA mice while muscle-specific SMN expression has no phenotypic effect
    Tatiana O Gavrilina
    Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH 43210, USA
    Hum Mol Genet 17:1063-75. 2008
    Spinal muscular atrophy (SMA) is caused by loss of the survival motor neuron gene (SMN1) and retention of the SMN2 gene. The copy number of SMN2 affects the amount of SMN protein produced and the severity of the SMA phenotype...
  98. doi Identification of a battery of tests for drug candidate evaluation in the SMNDelta7 neonate model of spinal muscular atrophy
    Bassem F El-Khodor
    PsychoGenics Inc, 765 Old Sawmill River Road, Tarrytown, NY 10591, USA
    Exp Neurol 212:29-43. 2008
    ..Loss of SMN1 is partially compensated by the copy gene, SMN2. Currently, there are no specific treatments for SMA...
  99. pmc Detection of human survival motor neuron (SMN) protein in mice containing the SMN2 transgene: applicability to preclinical therapy development for spinal muscular atrophy
    Virginia B Mattis
    Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA
    J Neurosci Methods 175:36-43. 2008
    ..SMA is caused by loss of the Survival Motor Neuron 1 (SMN1) gene, however, an identically coding gene called SMN2 is retained, but is alternatively spliced to produce approximately 90% truncated protein...
  100. doi Universal multiplex PCR and CE for quantification of SMN1/SMN2 genes in spinal muscular atrophy
    Chun Chi Wang
    School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
    Electrophoresis 30:1102-10. 2009
    We established a universal multiplex PCR and CE to calculate the copy number of survival motor neuron (SMN1 and SMN2) genes for clinical screening of spinal muscular atrophy (SMA)...

Research Grants43

  1. Judith A Steen; Fiscal Year: 2014
    ..two copies of the SMN gene, the telomeric SMN1, which encodes for a full-length form (FL-SMN), and the centromeric SMN2, which encodes primarily for a rapidly-degraded truncated form (SMN[unreadable]7) as well as the full-length form...
  2. Small Oligonucleotides As Therapeutic Agents Of Spinal Muscular Atrophy
    Ravindra N Singh; Fiscal Year: 2012
    ..A nearly identical copy of this gene, SMN2, fails to provide protection from SMA due to production of a truncated SMN because of skipping of SMN2 exon 7 ..
  3. High-affinity RNA targets of Survival Motor Neuron Protein
    Ravindra N Singh; Fiscal Year: 2013
    ..A nearly identical copy of the gene, SMN2, fails to compensate for the loss of SMN1 owing to predominant SMN2 exon 7 skipping that produces a truncated ..
  4. Arthur H M Burghes; Fiscal Year: 2014
    ..SMA is caused by loss of the SMN1 gene and retention of the SMN2 gene, leading to low levels of wild-type SMN, which is insufficient for motor neuron survival...
  5. Testing Compounds that Increase SMN levels for Efficacy in Mouse Models of SMA
    Elliot J Androphy; Fiscal Year: 2010
    ..A nearly identical copy gene, SMN2, fails to protect from development of SMA because its mRNA undergoes alternative splicing that produces a truncated,..
  6. Motor neuron generation from SMA patient-derived induced pluripotent stem cells
    Allison D Ebert; Fiscal Year: 2010
    ..Although humans have a second copy of SMN (SMN2), this gene contains a non-polymorphic C to T transition that produces an unstable, truncated protein lacking the ..
  7. Motoneuron-selective Rescue of SMA Model Mice
    Mendell Rimer; Fiscal Year: 2012
    ..This is explained by the presence of a second SMN gene in the human genome (SMN2)...
  8. Tetracycline derivatives as SMN2 mRNA splicing modifiers for treatment of SMA.
    S Ken Tanaka; Fiscal Year: 2013
    ..A nearly identical gene in humans, SMN2, fails to prevent SMA because its pre-mRNA undergoes aberrant splicing resulting in an unstable and non-functional ..
  9. Cooperative lead development program for treatment of spinal muscular atrophy
    Elliot J Androphy; Fiscal Year: 2012
    ..A nearly identical copy gene, SMN2, fails to protect from development of SMA because its mRNA undergoes alternative splicing of exon 7...
  10. Michelle L Hastings; Fiscal Year: 2014
    ..Humans have a second gene, SMN2, which is nearly identical to SMN1. Both SMN1 and SMN2 code for SMN protein...
  11. Christine J DiDonato; Fiscal Year: 2016
    ..SMA is caused by the loss of the survival motor neuron gene (SMN1). SMN2, a nearly identical copy gene, is present in all SMA patients but differs by a critical nucleotide that alters exon ..
  12. Testing Therapies in a New Mild SMA Mouse: A Model for Type II/III Patients
    Cathleen M Lutz; Fiscal Year: 2013
    ..the Burgheron model, which we generated by breeding a combination of alleles to achieve mice that have intermediate SMN2 levels...
  13. Zhongwei Du; Fiscal Year: 2014
    ..It is caused by mutations or deletions in the gene encoding the survival motor neuron protein (SMN)...
  14. Umrao Monani; Fiscal Year: 2016
    ..Residual protein is expressed from SMN2, a partially functional homologue of the SMN1 gene. There is presently no cure for SMA...
  15. CATHERINE DOMINGUEZ; Fiscal Year: 2015
    ..SMA is caused by low levels of survival motor neuron (SMN) protein. SMN is encoded by two genes, SMN1 and SMN2. SMN protein is required for survival and SMA is caused by deletions or mutations of SMN1, but early lethality of ..
  16. Electrophysiological phenotypes in a Drosophila model of SMA
    Subhabrata Sanyal; Fiscal Year: 2012
    ..disorders in humans, is due to the loss of the telomeric SMN1 gene and partial rescue by the centromeric homolog SMN2 which is similar to SMN1 but that, due to splicing errors, makes very little functional SMN protein...
  17. The Identification and Manipulation of RNA Splicing Factor Regulators in Spinal M
    MALLORY ANN HAVENS; Fiscal Year: 2013
    ..Humans have a second gene, SMN2, that also codes for SMN protein, albeit at much lower levels due to a splicing defect resulting in skipping of ..
  18. Ravindra N Singh; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): Humans have two copies of Survival of Motor Neuron (SMN) gene, SMN1 and SMN2. Loss of SMN1 leads to spinal muscular atrophy (SMA), a debilitating disease of infants and children...
  19. Determinants that regulate splicing of SMN
    Christian L Lorson; Fiscal Year: 2012
    ..Interestingly, a human-specific copy gene is present on the same region of chromosome 5q called SMN2. SMN2 is nearly identical to SMN1, however, mutations in SMN2 have no clinical consequence if SMN1 is retained...
  20. 15th Annual International Spinal Muscular Atrophy Research Group Meeting
    Jill Jarecki; Fiscal Year: 2011
    ..it is one of the neurological diseases closest to treatment, due to the unique presence of a back-up gene called SMN2, providing great therapeutic possibility...
  21. 14th Annual International Spinal Muscular Atrophy Research Group Meeting
    Jill Jarecki; Fiscal Year: 2010
    ..This is due to the unique presence of a back-up gene called SMN2, providing great translational possibility...
  22. 16th Annual International Spinal Muscular Atrophy Research Group Meeting
    Jill Jarecki; Fiscal Year: 2012
    ..it is one of the neurological diseases closest to treatment, due to the unique presence of a back-up gene called SMN2, providing great therapeutic possibility...
  23. 17th Annual International Spinal Muscular Atrophy Research Group Meeting
    Jill Jarecki; Fiscal Year: 2013
    ..it is one of the neurological diseases closest to treatment, due to the unique presence of a back-up gene called SMN2, which provides great therapeutic possibility...
  24. The Mouse SNM Gene: Potential Role in Modeling Spinal Muscular Atrophy
    JORDAN GLADMAN; Fiscal Year: 2009
    ..The SMN1 protein is necessary for motor neuron survival. The human genome contains a nearly identical gene. The SMN2 gene, however, is expressed at greatly reduced levels due to reduced processing of the SMN2 RNA product...
  25. The Electrophysiology of Motor Neuron Diseases
    Mark Bromberg; Fiscal Year: 2002
    ..Recent genetic studies in SMA indicate a relationship between survival motor neuron gene (SMN2) copy number and SMA type. Unanswered is the relationship between copy number and LMN number...
  26. 13th Annual International Spinal Muscular Atrophy Research Group Meeting
    Jill Jarecki; Fiscal Year: 2009
    ..Due to the unique presence of a back-up gene for SMN1 called SMN2, there is great translational possibility for the disease...
  27. Optimization of drug-like compounds for treatment of spinal muscular atrophy
    Elliot Androphy; Fiscal Year: 2009
    ..SMA results from homozygous mutation of the SMN (survival motor neuron) 1 gene. A nearly identical copy, SMN2, fails to protect from development of SMA as its major mRNA undergoes alternative splicing that encodes for an ..
  28. Design of molecules that promote SMN2 exon 7 inclusion
    ADRIAN KRAINER; Fiscal Year: 2005
    ..In humans, a second, nearly identical gene, SMN2, allows affected individuals to survive, but in most patients it cannot express sufficient amounts of active ..
  29. MOLECULAR PATHOGENESIS OF SPINAL MUSCULAR ATROPHY
    Elliot Androphy; Fiscal Year: 2004
    ..The centromeric 5q13 SMN2 gene encodes an identical protein...
  30. SMN associated proteins and compounds for SMA therapy
    Jianhua Zhou; Fiscal Year: 2005
    ..Due to a single nucleotide difference, T in the second gene SMN2 from C in SMNI, the majority of SMN2 mRNA or protein skips exon7, resulting in an unstable SMNA7 protein and ..
  31. Factors that regulate pre-mRNA processing of SMN
    Diane Hu; Fiscal Year: 2005
    ..A nearly identical gene, SMN2, is present in SMA patients although it cannot provide protection from SMA development even though SMN1 and SMN2 ..
  32. SMN2 Silent Mutation Knock-in: New SMA Mouse Model-Better Therapies
    DAWN CHANDLER; Fiscal Year: 2008
    ..The SMN1 protein is necessary for motor neuron survival. The human genome harbors a nearly identical gene, SMN2, that is functionally redundant with SMN1 and could potentially rescue the disease phenotype...
  33. Regulation of the survival motor neuron gene
    CHARLOTTE SUMNER; Fiscal Year: 2008
    ..All patients retain a second copy of the gene (SMN2) that produces insufficient quantities of SMN protein to fully compensate for the loss of SMN1...
  34. Targeting a novel silencer to correct SMN2 splicing in Spinal Muscular Atrophy
    Ravindra Singh; Fiscal Year: 2007
    ..A nearly identical copy of the gene, SMN2, that produces nonfunctional SMN protein due to skipping of exon 7, fails to compensate for the loss of SMN1...
  35. Determinants that regulate splicing of SMN
    Christian L Lorson; Fiscal Year: 2010
    ..A nearly identical copy gene exists, SMN2, however, it cannot provide protection from disease development in the absence of SMN1...
  36. Role of metallothioneins in hepatocellular carcinoma
    Samson Jacob; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  37. CLINICAL TRIALS FOR PEDIATRIC SPINAL MUSCULAR ATROPHY
    Susan Iannaccone; Fiscal Year: 2005
    ..Blood samples for DNA (SMN2 copy count) and SMN mRNA and buccal smear for SMN protein will be obtained...
  38. Creation of hypomorphic panel of Smn mice that mimic human SMN2 splicing
    CHRISTINE DIDONATO; Fiscal Year: 2008
    ..b>SMN2, a nearly identical gene is present in all SMA patients; however, it cannot provide protection from disease due to ..
  39. Spinal Muscular Atrophy-- SMNs role in motor neurons
    Arthur Burghes; Fiscal Year: 2004
    ..SMA is caused by the loss, or mutation, of the Survival Motor Neuron 1 gene (SMN1) and retention of the SMN2 gene. Both genes are ubiquitously expressed, but the majority of the product from the SMN2 gene lacks exon 7...
  40. DNA METHYLATION AND GENE EXPRESSION IN CANCER CELLS
    Samson Jacob; Fiscal Year: 2004
    ..It is hoped that this study could provide the impetus to explore ways to reactivate these repressed genes that may result in the arrest of specific neoplastic growth. ..
  41. MOLECULAR MECHANISMS OF METALLOTHIONEIN INDUCTION
    Samson Jacob; Fiscal Year: 2003
    ..Because MT induction is repressed in many cancer cells due to hypermethylation, the re-expresssion of MT may be one effective means to arrest malignant growth of these cells. ..
  42. Funding for FightSMA Researchers' Conference in Washington, DC, April 2008
    Christian Lorson; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  43. Alcohol-induced epigenetic changes in the liver genome
    Samson Jacob; Fiscal Year: 2007
    ..This proposal also fits well with the mission of the National Institute of Alcohol Abuse and Alcoholism on "alcohol metabolism and epigenetic effects on tissue injury". [unreadable] [unreadable] [unreadable]..