Abstract:
:Spinal muscular atrophy (SMA), a genetic neurodegenerative disorder, is caused by mutations or deletions in the survival of motor neuron 1 (SMN1) gene that result in SMN deficiency. SMN deficiency impairs microtubule networks in Smn-deficient cells and in SMA-like motor neuron cultures. Microtubule defects can be restored by knockdown of the stathmin gene (Stmn), which is upregulated in SMA. However, whether in vivo reduction of stathmin levels could improve the pathology of SMA has not been investigated. Here we generated SMA-like mice in a Stmn knockout (KO) background through a series of genetic crosses. Analyses of motor performance and histology showed that heterozygous StmnKO (Stmn(+/-)) but not homozygous StmnKO (Stmn(-/-)) ameliorates some SMA defects, with increased microtubule densities in sciatic axons, improved motor performance, enhanced NMJ maturation, and mitigated neuroinflammation. However, Stmn deletion does not prolong the lifespan of SMA-like mice, suggesting that stathmin dysregulation and microtubule disruption are not a cause but rather a consequence of SMA pathology. This work demonstrates that limiting the amount of stathmin in SMA-like mice is effective in reducing their neuromuscular defects, whereas induced aberrant expression of stathmin in SMA-like animals is detrimental.
journal_name
Neurobiol Disjournal_title
Neurobiology of diseaseauthors
Wen HL,Ting CH,Liu HC,Li H,Lin-Chao Sdoi
10.1016/j.nbd.2012.11.015subject
Has Abstractpub_date
2013-04-01 00:00:00pages
94-103eissn
0969-9961issn
1095-953Xpii
S0969-9961(12)00378-6journal_volume
52pub_type
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pub_type: 杂志文章,评审
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journal_title:Neurobiology of disease
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journal_title:Neurobiology of disease
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doi:10.1016/j.nbd.2012.10.001
更新日期:2013-03-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2013.12.019
更新日期:2014-05-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2014.01.013
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doi:10.1016/j.nbd.2015.04.014
更新日期:2015-07-01 00:00:00
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journal_title:Neurobiology of disease
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abstract::Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an excessive expansion of a CAG trinucleotide repeat in the gene encoding the protein huntingtin, resulting in an elongated stretch of glutamines near the N-terminus of the protein. Here we report the derivation of a collection of ...
journal_title:Neurobiology of disease
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journal_title:Neurobiology of disease
pub_type: 杂志文章
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journal_title:Neurobiology of disease
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pub_type: 杂志文章
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