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Genes Dev 2005 Oct 01;1919:2320-30. doi: 10.1101/gad.342005.
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Reduced U snRNP assembly causes motor axon degeneration in an animal model for spinal muscular atrophy.

Winkler C , Eggert C , Gradl D , Meister G , Giegerich M , Wedlich D , Laggerbauer B , Fischer U .

Spinal muscular atrophy (SMA) is a motoneuron disease caused by reduced levels of survival motoneuron (SMN) protein. Previous studies have assigned SMN to uridine-rich small nuclear ribonucleoprotein particle (U snRNP) assembly, splicing, transcription, and RNA localization. Here, we have used gene silencing to assess the effect of SMN protein deficiency on U snRNP metabolism in living cells and organisms. In HeLa cells, we show that reduction of SMN to levels found in SMA patients impairs U snRNP assembly. In line with this, induced silencing of SMN expression in Xenopus laevis or zebrafish arrested embryonic development. Under less severe knock-down conditions, zebrafish embryos proceeded through development yet exhibited dramatic SMA-like motor axon degeneration. The same was observed after silencing two other essential factors in the U snRNP assembly pathway, Gemin2 and pICln. Importantly, the injection of purified U snRNPs into either SMN- or Gemin2-deficient embryos of Xenopus and zebrafish prevented developmental arrest and motoneuron degeneration, respectively. These findings suggest that motoneuron degeneration in SMA patients is a direct consequence of impaired production of U snRNPs.

PubMed ID: 16204184
PMC ID: PMC1240041
Article link: Genes Dev

Species referenced: Xenopus laevis
Genes referenced: acta2 gemin2 smn1 syt2
Antibodies: Syt2 Ab1

Disease Ontology terms: spinal muscular atrophy

Article Images: [+] show captions
References [+] :
Appel, Motoneuron fate specification revealed by patterned LIM homeobox gene expression in embryonic zebrafish. 1996, Pubmed