title: SMN deficiency disrupts brain development in a mouse model of severe spinal muscular atrophy.
abstract: Reduced expression of the survival motor neuron (SMN) gene causes the childhood motor neuron disease spinal muscular atrophy (SMA). Low levels of ubiquitously expressed SMN protein result in the degeneration of lower motor neurons, but it remains unclear whether other regions of the nervous system are also affected. Here we show that reduced levels of SMN lead to impaired perinatal brain development in a mouse model of severe SMA. Regionally selective changes in brain morphology were apparent in areas normally associated with higher SMN levels in the healthy postnatal brain, including the hippocampus, and were associated with decreased cell density, reduced cell proliferation and impaired hippocampal neurogenesis. A comparative proteomics analysis of the hippocampus from SMA and wild-type littermate mice revealed widespread modifications in expression levels of proteins regulating cellular proliferation, migration and development when SMN levels were reduced. This study reveals novel roles for SMN protein in brain development and maintenance and provides the first insights into cellular and molecular pathways disrupted in the brain in a severe form of SMA.
authors: Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh Medical School, Edinburgh, UK.
authors: Thomas M
authors: TM
authors: Wishart
authors: Jack P-W
authors: JP
authors: Huang
authors: Lyndsay M
authors: LM
authors: Murray
authors: Douglas J
authors: DJ
authors: Lamont
authors: Chantal A
authors: CA
authors: Mutsaers
authors: Jenny
authors: J
authors: Ross
authors: Pascal
authors: P
authors: Geldsetzer
authors: Olaf
authors: O
authors: Ansorge
authors: Kevin
authors: K
authors: Talbot
authors: Simon H
authors: SH
authors: Parson
authors: Thomas H
authors: TH
authors: Gillingwater
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D004195:Disease Models, Animal; D006624:Hippocampus / Q000254:growth & development*; D051379:Mice; D018345:Mice, Knockout; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D040901:Proteomics; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics*
chemical_list: C526472:Smn1 protein, mouse; D055533:Survival of Motor Neuron 1 Protein