No widespread induction of cell death genes occurs in pure motoneurons in an amyotrophic lateral sclerosis mouse model.
Hum Mol Genet
; 14(21): 3309-20, 2005 Nov 01.
Article
en En
| MEDLINE
| ID: mdl-16192287
ABSTRACT
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 SOD1(G93A) 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 SOD1(G93A) motoneurons during disease progression and unexpectedly, no widespread induction of cell death-associated genes was detected in motoneurons of SOD1(G93A) mice.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Regulación de la Expresión Génica
/
Apoptosis
/
Perfilación de la Expresión Génica
/
Proteínas Reguladoras de la Apoptosis
/
Esclerosis Amiotrófica Lateral
/
Neuronas Motoras
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Hum Mol Genet
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
2005
Tipo del documento:
Article
País de afiliación:
Suiza