title: Gene targeting of Gemin2 in mice reveals a correlation between defects in the biogenesis of U snRNPs and motoneuron cell death.
abstract: 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.
authors.affiliation: Institute of Clinical Neurobiology, Josef-Schneider Strasse 11, D-97080 Würzburg, Germany.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Jablonka
authors.forename: Bettina
authors.initials: B
authors.lastname: Holtmann
authors.forename: Gunter
authors.initials: G
authors.lastname: Meister
authors.forename: Michael
authors.initials: M
authors.lastname: Bandilla
authors.forename: Wilfried
authors.initials: W
authors.lastname: Rossoll
authors.forename: Utz
authors.initials: U
authors.lastname: Fischer
authors.forename: Michael
authors.initials: M
authors.lastname: Sendtner
mesh_terms: 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
chemical_list: 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