Jablonka Sibylle, Holtmann Bettina, Meister Gunter, Bandilla Michael, Rossoll Wilfried, Fischer Utz, Sendtner Michael
Institute of Clinical Neurobiology, Josef-Schneider Strasse 11, D-97080 Würzburg, Germany.
Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):10126-31. doi: 10.1073/pnas.152318699. Epub 2002 Jun 28.
Neuronal degeneration in spinal muscular atrophy is caused by reduced expression of the survival motor neuron (SMN) protein. SMN and the tightly interacting Gemin2 form part of a macromolecular complex (SMN complex) that mediates assembly of spliceosomal small nuclear ribonucleoproteins (U snRNPs). We used mouse genetics to investigate the function of this complex in motoneuron maintenance. Reduced Smn/Gemin2 protein levels lead to disturbed U snRNP assembly as indicated by reduced nuclear accumulation of Sm proteins. This finding correlates with enhanced motoneuron degeneration in Gemin2(+/-)/Smn(+/-) mice. Our data provide in vivo evidence that impaired production of U snRNPs contributes to motoneuron degeneration.
脊髓性肌萎缩症中的神经元变性是由存活运动神经元（SMN）蛋白表达减少所致。SMN与紧密相互作用的Gemin2构成一个大分子复合物（SMN复合物）的一部分，该复合物介导剪接体小核核糖核蛋白（U snRNP）的组装。我们利用小鼠遗传学来研究该复合物在运动神经元维持中的功能。Smn/Gemin2蛋白水平降低导致U snRNP组装紊乱，这表现为Sm蛋白的核内积累减少。这一发现与Gemin2(+/-)/Smn(+/-)小鼠中运动神经元变性增强相关。我们的数据提供了体内证据，表明U snRNP产生受损导致运动神经元变性。
