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Autosomal recessive proximal spinal muscular atrophy (SMA) is a severe neurodegenerative disease of childhood causing weakness and wasting secondary to motor neuron dysfunction. Over 97% of cases are caused by deletions or mutations within the survival motor neuron (SMN) gene. The SMN protein is highly expressed within brain, spinal cord and muscle, and is decreased in SMA patients. It has been shown to have an important role in RNA metabolism, but the reason for the specific motor neuron loss is still unclear. We have used a novel antibody array technology to look for differences in the expression patterns of primary muscle cultures from a type II SMA patient and a normal control. A relatively small number of differences were found within a group of proteins that function as both RNA binding proteins and transcription factors. Interactions between a number of these proteins are well established, and three of them bind in turn to p53 which interacts with SMN. A number of the changes were confirmed with western blot analysis both in the primary muscle cultures and in skeletal muscle samples from SMA patients and controls. Changes at the mRNA level were also confirmed with oligonucleotide arrays. These results suggest that a common transcription pathway may be altered in the disease state, and suggests that down-regulation of transcription factors contributes to SMA pathogenesis.

Original publication

DOI

10.1093/brain/awg208

Type

Journal article

Journal

Brain

Publication Date

09/2003

Volume

126

Pages

2052 - 2064

Keywords

Adolescent, Adult, Blotting, Western, Cells, Cultured, Cyclic AMP Response Element-Binding Protein, Female, Gene Expression, Humans, Immunoassay, Male, Models, Biological, Muscle Proteins, Muscle, Skeletal, Muscular Atrophy, Spinal, Nerve Tissue Proteins, Oligonucleotide Array Sequence Analysis, Proteomics, RNA, Messenger, RNA-Binding Proteins, SMN Complex Proteins