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Disruption of SMN function by ectopic expression of the human SMN gene in Drosophila
Author(s) -
Miguel-Aliaga Irene,
Chan Yick Bun,
Davies Kay E.,
van den Heuvel Marcel
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)02243-2
Subject(s) - ectopic expression , biology , microbiology and biotechnology , gene , spinal muscular atrophy , function (biology) , mutation , genetics , gene expression
Spinal muscular atrophy is a neurodegenerative disorder caused by mutations or deletions in the survival motor neuron ( SMN ) gene. We have cloned the Drosophila ortholog of SMN (DmSMN) and disrupted its function by ectopically expressing human SMN. This leads to pupal lethality caused by a dominant‐negative effect, whereby human SMN may bind endogenous DmSMN resulting in non‐functional DmSMN/human SMN hetero‐complexes. Ectopic expression of truncated versions of DmSMN and yeast two‐hybrid analysis show that the C‐terminus of SMN is necessary and sufficient to replicate this effect. We have therefore generated a system which can be utilized to carry out suppressor and high‐throughput screens, and provided in vivo evidence for the importance of SMN oligomerization for SMN function at the level of an organism as a whole.