Reduced survival motor neuron (Smn) gene dose in mice leads to motor neuron degeneration: an animal model for spinal muscular atrophy type III - PubMed (original) (raw)

. 2000 Feb 12;9(3):341-6.

doi: 10.1093/hmg/9.3.341.

Affiliations

• PMID: 10655542
• DOI: 10.1093/hmg/9.3.341

Reduced survival motor neuron (Smn) gene dose in mice leads to motor neuron degeneration: an animal model for spinal muscular atrophy type III

S Jablonka et al. Hum Mol Genet. 2000.

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.

PubMed Disclaimer

Similar articles

• The human centromeric survival motor neuron gene (SMN2) rescues embryonic lethality in Smn(-/-) mice and results in a mouse with spinal muscular atrophy.
  Monani UR, Sendtner M, Coovert DD, Parsons DW, Andreassi C, Le TT, Jablonka S, Schrank B, Rossoll W, Prior TW, Morris GE, Burghes AH. Monani UR, et al. Hum Mol Genet. 2000 Feb 12;9(3):333-9. doi: 10.1093/hmg/9.3.333. Hum Mol Genet. 2000. PMID: 10655541
• 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?
  Rossoll W, Kröning AK, Ohndorf UM, Steegborn C, Jablonka S, Sendtner M. Rossoll W, et al. Hum Mol Genet. 2002 Jan 1;11(1):93-105. doi: 10.1093/hmg/11.1.93. Hum Mol Genet. 2002. PMID: 11773003
• Aclarubicin treatment restores SMN levels to cells derived from type I spinal muscular atrophy patients.
  Andreassi C, Jarecki J, Zhou J, Coovert DD, Monani UR, Chen X, Whitney M, Pollok B, Zhang M, Androphy E, Burghes AH. Andreassi C, et al. Hum Mol Genet. 2001 Nov 15;10(24):2841-9. doi: 10.1093/hmg/10.24.2841. Hum Mol Genet. 2001. PMID: 11734549
• [Spinal muscular atrophy: SMN protein deficiency].
  Jedrzejowska M. Jedrzejowska M. Neurol Neurochir Pol. 2001 Mar-Apr;35(2):289-97. Neurol Neurochir Pol. 2001. PMID: 11599226 Review. Polish.
• Congenital bone fractures in spinal muscular atrophy: functional role for SMN protein in bone remodeling.
  Shanmugarajan S, Swoboda KJ, Iannaccone ST, Ries WL, Maria BL, Reddy SV. Shanmugarajan S, et al. J Child Neurol. 2007 Aug;22(8):967-73. doi: 10.1177/0883073807305664. J Child Neurol. 2007. PMID: 17761651 Free PMC article. Review.

Cited by

• Nusinersen ameliorates motor function and prevents motoneuron Cajal body disassembly and abnormal poly(A) RNA distribution in a SMA mouse model.
  Berciano MT, Puente-Bedia A, Medina-Samamé A, Rodríguez-Rey JC, Calderó J, Lafarga M, Tapia O. Berciano MT, et al. Sci Rep. 2020 Jul 1;10(1):10738. doi: 10.1038/s41598-020-67569-3. Sci Rep. 2020. PMID: 32612161 Free PMC article.
• A transgene carrying an A2G missense mutation in the SMN gene modulates phenotypic severity in mice with severe (type I) spinal muscular atrophy.
  Monani UR, Pastore MT, Gavrilina TO, Jablonka S, Le TT, Andreassi C, DiCocco JM, Lorson C, Androphy EJ, Sendtner M, Podell M, Burghes AH. Monani UR, et al. J Cell Biol. 2003 Jan 6;160(1):41-52. doi: 10.1083/jcb.200208079. Epub 2003 Jan 6. J Cell Biol. 2003. PMID: 12515823 Free PMC article.
• Neurochondrin interacts with the SMN protein suggesting a novel mechanism for spinal muscular atrophy pathology.
  Thompson LW, Morrison KD, Shirran SL, Groen EJN, Gillingwater TH, Botting CH, Sleeman JE. Thompson LW, et al. J Cell Sci. 2018 Apr 17;131(8):jcs211482. doi: 10.1242/jcs.211482. J Cell Sci. 2018. PMID: 29507115 Free PMC article.
• Neurotransmitter release in motor nerve terminals of a mouse model of mild spinal muscular atrophy.
  Ruiz R, Tabares L. Ruiz R, et al. J Anat. 2014 Jan;224(1):74-84. doi: 10.1111/joa.12038. Epub 2013 Mar 13. J Anat. 2014. PMID: 23489475 Free PMC article.
• Gene targeting of Gemin2 in mice reveals a correlation between defects in the biogenesis of U snRNPs and motoneuron cell death.
  Jablonka S, Holtmann B, Meister G, Bandilla M, Rossoll W, Fischer U, Sendtner M. Jablonka S, et al. Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):10126-31. doi: 10.1073/pnas.152318699. Epub 2002 Jun 28. Proc Natl Acad Sci U S A. 2002. PMID: 12091709 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Silverchair Information Systems

• Other Literature Sources

  • The Lens - Patent Citations Database

• Molecular Biology Databases

  • Mouse Genome Informatics (MGI)