Journal Article

SMN deficiency disrupts brain development in a mouse model of severe spinal muscular atrophy

Thomas M. Wishart, Jack P.-W. Huang, Lyndsay M. Murray, Douglas J. Lamont, Chantal A. Mutsaers, Jenny Ross, Pascal Geldsetzer, Olaf Ansorge, Kevin Talbot, Simon H. Parson and Thomas H. Gillingwater

in Human Molecular Genetics

Volume 19, issue 21, pages 4216-4228
Published in print November 2010 | ISSN: 0964-6906
Published online August 2010 | e-ISSN: 1460-2083 | DOI:
SMN deficiency disrupts brain development in a mouse model of severe spinal muscular atrophy

Show Summary Details


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.

Journal Article.  7373 words.  Illustrated.

Subjects: Genetics and Genomics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.