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.
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
- Dysregulation of innate immune signaling in animal models of spinal muscular atrophy.
Garcia EL, Steiner RE, Raimer AC, Herring LE, Matera AG, Spring AM. Garcia EL, et al. BMC Biol. 2024 Apr 25;22(1):94. doi: 10.1186/s12915-024-01888-z. BMC Biol. 2024. PMID: 38664795 Free PMC article. - The contribution and therapeutic implications of IGHMBP2 mutations on IGHMBP2 biochemical activity and ABT1 association.
Vadla GP, Singh K, Lorson CL, Lorson MA. Vadla GP, et al. Biochim Biophys Acta Mol Basis Dis. 2024 Apr;1870(4):167091. doi: 10.1016/j.bbadis.2024.167091. Epub 2024 Feb 24. Biochim Biophys Acta Mol Basis Dis. 2024. PMID: 38403020 - SMN Is Physiologically Downregulated at Wild-Type Motor Nerve Terminals but Aggregates Together with Neurofilaments in SMA Mouse Models.
Franco-Espin J, Gatius A, Armengol JÁ, Arumugam S, Moradi M, Sendtner M, Calderó J, Tabares L. Franco-Espin J, et al. Biomolecules. 2022 Oct 20;12(10):1524. doi: 10.3390/biom12101524. Biomolecules. 2022. PMID: 36291733 Free PMC article. - Therapy development for spinal muscular atrophy: perspectives for muscular dystrophies and neurodegenerative disorders.
Jablonka S, Hennlein L, Sendtner M. Jablonka S, et al. Neurol Res Pract. 2022 Jan 4;4(1):2. doi: 10.1186/s42466-021-00162-9. Neurol Res Pract. 2022. PMID: 34983696 Free PMC article. Review. - In Search of a Cure: The Development of Therapeutics to Alter the Progression of Spinal Muscular Atrophy.
Ojala KS, Reedich EJ, DiDonato CJ, Meriney SD. Ojala KS, et al. Brain Sci. 2021 Feb 5;11(2):194. doi: 10.3390/brainsci11020194. Brain Sci. 2021. PMID: 33562482 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases