Gene targeting of Gemin2 in mice reveals a correlation between defects in the biogenesis of U snRNPs and motoneuron cell death.
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.
Jablonka
Sibylle
S
Institute of Clinical Neurobiology, Josef-Schneider Strasse 11, D-97080 Würzburg, Germany.
Holtmann
Bettina
B
Meister
Gunter
G
Bandilla
Michael
M
Rossoll
Wilfried
W
Fischer
Utz
U
Sendtner
Michael
M
D000818:Animals; D016923:Cell Death; D017362:Cyclic AMP Response Element-Binding Protein; D004195:Disease Models, Animal; D018390:Gene Targeting; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000473:pathology*; D009134:Muscular Atrophy, Spinal / Q000235:genetics / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016601:RNA-Binding Proteins; D015183:Restriction Mapping; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics; D055532:SMN Complex Proteins
D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D017411:Ribonucleoproteins, Small Nuclear; D055532:SMN Complex Proteins; C491561:Sip1 protein, mouse