Expression profiling in spinal muscular atrophy reveals an RNA binding protein deficit

Neuromuscul Disord. 2004 Nov;14(11):711-22. doi: 10.1016/j.nmd.2004.08.009.

Abstract

Spinal muscular atrophy is a common neuromuscular disorder caused by deletions or mutations within the survival motor neuron gene. The reason for specific motor neuron loss within the disease is still unclear. Expression profiling has been carried out in two models of spinal muscular atrophy; the heterozygote mouse model and human primary muscle cultures from a spinal muscular atrophy patient. A group of RNA binding proteins are up-regulated in spinal muscular atrophy motor neurons. One such protein, BRUNOL3, is highly expressed within spinal cord and muscle and also at the same developmental stage as survival motor neuron. The differential expression of Brunol3 has been confirmed with real-time RT-PCR in spinal cord and muscle of three different models of spinal muscular atrophy. BRUNOL3 has been shown to co-localise with survival motor neuron in the nuclei of neuronal cells and to co-immunoprecipitate with Smn in mouse brain. This is the first time that a link has been established between RNA binding proteins and survival motor neuron within motor neurons.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Animals
  • Blotting, Western / methods
  • Brain / cytology
  • Brain / metabolism
  • CELF Proteins
  • Cells, Cultured
  • Cyclic AMP Response Element-Binding Protein
  • Embryo, Mammalian
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation / physiology*
  • Humans
  • Immunoprecipitation / methods
  • In Situ Hybridization / methods
  • Male
  • Mice
  • Motor Neurons
  • Muscle, Skeletal / metabolism
  • Muscular Atrophy, Spinal / genetics
  • Muscular Atrophy, Spinal / metabolism*
  • Nerve Tissue Proteins / metabolism
  • Oligonucleotide Array Sequence Analysis / methods
  • Pregnancy
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • SMN Complex Proteins
  • Spinal Cord / cytology
  • Spinal Cord / metabolism

Substances

  • CELF Proteins
  • CELF2 protein, human
  • Cyclic AMP Response Element-Binding Protein
  • Nerve Tissue Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • SMN Complex Proteins