Gene targeting of Gemin2 in mice reveals a correlation between defects in the biogenesis of U snRNPs and motoneuron cell death

被引：66

作者：

Jablonka, S

Holtmann, B

Meister, G

Bandilla, M

Rossoll, W

Fischer, U

Sendtner, M

机构：

[1] Inst Clin Neurobiol, D-97080 Wurzburg, Germany

[2] Max Planck Inst Biochem, D-82152 Martinsried, Germany

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2002年 / 99卷 / 15期

关键词：

D O I：

10.1073/pnas.152318699

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 spliceo-somal 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.

引用

收藏

页码：10126 / 10131

页数：6

相关论文

共 34 条

[21] The Caenorhabditis elegans orthologue of the human gene responsible for spinal muscular atrophy is a maternal product critical for germline maturation and embryonic viability [J].

Miguel-Aliaga, I ;

Culetto, E ;

Walker, DS ;

Baylis, HA ;

Sattelle, DB ;

Davies, KE .

HUMAN MOLECULAR GENETICS, 1999, 8 (12) :2133-2143

[22] Disruption of SMN function by ectopic expression of the human SMN gene in Drosophila [J].

Miguel-Aliaga, I ;

Chan, YB ;

Davies, KE ;

van den Heuvel, M .

FEBS LETTERS, 2000, 486 (02) :99-102

[23] The human centromeric survival motor neuron gene (SMN2) rescues embryonic lethality in Smn-/- mice and results in a mouse with spinal muscular atrophy [J].

Monani, UR ;

Sendtner, M ;

Coovert, DD ;

Parsons, DW ;

Andreassi, C ;

Le, TT ;

Jablonka, S ;

Schrank, B ;

Rossol, W ;

Prior, TW ;

Morris, GE ;

Burghes, AHM .

HUMAN MOLECULAR GENETICS, 2000, 9 (03) :333-339

[24] The survival motor neuron protein of Schizosacharomyces pombe -: Conservation of survival motor neuron interaction domains in divergent organisms [J].

Paushkin, S ;

Charroux, B ;

Abel, L ;

Perkinson, RA ;

Pellizzoni, L ;

Dreyfuss, G .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (31) :23841-23846

[25] SMN mutants of spinal muscular atrophy patients are defective in binding to snRNP proteins [J].

Pellizzoni, L ;

Charroux, B ;

Dreyfuss, G .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (20) :11167-11172

[26] A novel function for SMN, the spinal muscular atrophy disease gene product, in pre-mRNA splicing [J].

Pellizzoni, L ;

Kataoka, N ;

Charroux, B ;

Dreyfuss, G .

CELL, 1998, 95 (05) :615-624

[27] Purification of native survival of motor neurons complexes and identification of Gemin6 as a novel component [J].

Pellizzoni, L ;

Baccon, J ;

Rappsilber, J ;

Mann, M ;

Dreyfuss, G .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (09) :7540-7545

[28] SMN gene duplication and the emergence of the SMN2 gene occurred in distinct hominids:: SMN2 is unique to Homo sapiens [J].

Rochette, CF ;

Gilbert, N ;

Simard, LR .

HUMAN GENETICS, 2001, 108 (03) :255-266

[29] Inactivation of the survival motor neuron gene, a candidate gene for human spinal muscular atrophy, leads to massive cell death in early mouse embryos [J].

Schrank, B ;

Gotz, R ;

Gunnersen, JM ;

Ure, JM ;

Toyka, KV ;

Smith, AG ;

Sendtner, M .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (18) :9920-9925

[30]

VERNET M, 1993, METHOD ENZYMOL, V225, P434

← 1 2 3 4 →