Genome-wide expression analysis of a spinal muscular atrophy model: towards discovery of new drug targets.
Spinal Muscular Atrophy is a recessive genetic disease and affects lower motor neurones and muscle tissue. A single gene is disrupted in SMA: SMN1 activity is abolished but a second copy of the gene (SMN2) provides limited activity. While the SMN protein has been shown to function in the assembly of RNA-protein complexes, it is unclear how the overall reduction in SMN activity specifically results in the neuromuscular phenotypes. Similar to humans, reduced smn activity in the fly causes earliest phenotypes in neuromuscular tissues. To uncover the effects of reduced SMN activity, we have studied gene expression in control and diseased fly tissues using whole genome micro-arrays. A number of gene expression changes are recovered and independently validated. Identified genes show trends in their predicted function: several are consistent with the function of SMN, in addition some uncover novel pathways. This and subsequent genetic analysis in the fly indicates some of the identified genes could be taken for further studies as potential drug targets for SMA and other neuromuscular disorders.
Lee
Sheena
S
OXION Initiative, Oxford Centre for Gene Function, Department of Human Anatomy and Genetics, University of Oxford, Oxford, United Kingdom. sheena.lee@dpag.ox.ac.uk
Sayin
Arzu
A
Cauchi
Ruben J
RJ
Grice
Stuart
S
Burdett
Howard
H
Baban
Dilair
D
van den Heuvel
Marcel
M
D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics; D004175:Diptera; D004195:Disease Models, Animal; D016678:Genome; D006801:Humans; D009134:Muscular Atrophy, Spinal / Q000188:drug therapy / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D016601:RNA-Binding Proteins / Q000235:genetics; D055532:SMN Complex Proteins; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein
D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526471:SMN1 protein, human; C526477:SMN2 protein, human; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein