Human Molecular Genetics Advance Access originally published online on September 28, 2005
Human Molecular Genetics 2005 14(21):3309-3320; doi:10.1093/hmg/ddi357
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No widespread induction of cell death genes occurs in pure motoneurons in an amyotrophic lateral sclerosis mouse model
1Department of Basic Neuroscience, Faculty of Medicine and 2Genomics Platform, National Center of Competence in Research ‘Frontiers in Genetics’, 1211 Geneva 4, Switzerland
* To whom correspondence should be addressed at: Department of Basic Neuroscience, Centre Médical Universitaire, 1 rue Michel Servet, 1211 Geneva 4, Switzerland. Tel: +41 223795446; Fax: +41 223795452; Email: ann.kato{at}medecine.unige.ch
Received August 25, 2005; Accepted September 23, 2005
To identify candidate genes that may be involved in motoneuron degeneration, we combined laser capture microdissection with microarray technology. Gene expression in motoneurons was analyzed during the progression of the disease in transgenic SOD1G93A mice that develop motoneuron loss. Three major observations were made: first, there was only a small number of genes that were differentially expressed in motoneurons at a pre-symptomatic age (27 out of 34 000 transcripts). Secondly, there is an early specific up-regulation of the gene coding for the intermediate filament vimentin that is increased even further during disease progression. Using in situ hybridization and immunohistochemical analysis, we show that vimentin expression was not only elevated in motoneurons but that the protein formed inclusions in the motoneuron cytoplasm. Thirdly, a time-course analysis of the motoneurons at a symptomatic age (90 and 120 days) showed a modest de-regulation of only a few genes associated with cell death pathways; however, a massive up-regulation of genes involved in cell growth and/or maintenance was observed. This is the first description of the gene profile of SOD1G93A motoneurons during disease progression and unexpectedly, no widespread induction of cell death-associated genes was detected in motoneurons of SOD1G93A mice.
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