Ongoing research at Solomon Park Research Institute

• In the search for an etiology of motor neuron disease (MND) also known as amyotrophic lateral sclerosis (ALS), three questions challenge any proposed cause. Why are motor neurons specifically affected? How does the degeneration in these cells spread from a primary site? Why is the condition irreversible?

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Papers published:

• Murine Spinal Cord Transcriptome Analysis Following Reduction of Prevalent Myelin cDNA Sequences
  Cellular and Molecular Neurobiology (in press)
  
  From 1000 randomly selected colonies from cDNA libraries derived from murine spinal cord subtracted against white matter by means of suppression subtractive hybridization, 220 clones were identified as differentially expressed by dot blot analysis. Sequence analysis by the BLAST programming identified 140 unique genes.
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• Spinal Cord Transcriptome Analysis Using Suppression Subtractive Hybridization and Mirror Orientation Selection
  Cellular and Molecular Neurobiology, Volume 26, Number 3, May 2006, pp. 259-275(17)
  
  Comparison of cDNA libraries derived from the spinal cord with those derived from the visual cortex by means of forward and reverse subtractive hybridization resulted in the cataloguing of 60 genes differentially expressed in the spinal cord.
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Presentations at conferences / symposiums:

• Systematic Elimination of Prevalent Myelin Sequences from Mouse Spinal Cord cDNA Preparations
  Lathia K. B., Yan Z. and Clapshaw P. A.
  
  Presented at: 17th International Symposium on ALSA/MND
  
  Background: We have previously demonstrated by suppression subtractive hybridization (SSH) and mirror orientation selection (MOS) that a large portion of sequences differentiating spinal cord from visual cortex in the mouse can be attributed to cDNA derived from myelin.  Fully half of all up-regulated sequences in the spinal cord subtracted against visual cortex are of glial cell origin.  Proteolipid protein alone accounts for some forty per cent of all up-regulated sequences in the spinal cord.  It is possible, although unlikely, that these differences reflect increased numbers of glial cells in this structure or possibly the ongoing metabolic activity of these cells normally present; however, it is desirable to design procedures that will allow the study of the transcription of mRNA in motor neurons unobstructed by the overwhelming presence of glial derived sequences.
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• Spinal Cord Transcriptome Analyzed By Suppression Subtractive Hybridization And Mirror Orientation Selection
  Lathia K. B., Yan Z. and Clapshaw P. A.
  
  Presented at: 37th Annual ASN Conference
  
  Background: Analysis of the transcriptome in motor neurons, the cells traditionally associated with motor neuron disease (MND)also known as amyotrophic lateral sclerosis (ALS), is hampered both by the diversity of the cell types in nervous tissue as well as the masking of the neural elements by the overwhelming glial matrix surrounding these cells.  Additionally, it is not known if the occurrence of such conditions as MND can be attributed to the motor neurons alone or are a product of external influences on these cells such as would be found in the surrounding glial cells.  Using a combination of suppression subtractive hybridization (SSH) and mirror orientation subtraction (MOS), we have constructed a library of expressed genes that are spinal cord specific. 
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• Up-Regulation of Genes in Murine Spinal Cord Transcriptome
  Yan Z., Lathia K. B. and Clapshaw P. A.
  
  Presented at: 16th International Symposium on ALSA/MND
  
  Background: Analysis of the transcriptome in motor neurons, the cells traditionally associated with amyotrophic lateral sclerosis, is hampered both by the diversity of the cell types in nervous tissue as well as the cloaking of the neural elements by the overwhelming glial matrix surrounding these cells. Using a combination of suppression subtractive hybridization (SSH) and mirror orientation selection (MOS), we have constructed a cDNA library of differentially expressed genes that are up-regulated in spinal cord.
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• Identification of Differentially Expressed Genes in Spinal Cord using Suppression Subtractive Hybridization
  Lathia K. B, Yan Z. and Clapshaw P. A
  
  Presented at: 15th International Symposium on ALSA/MND
  
  Background: Motor neurons, the cells traditionally associated with Amyotrophic Lateral Sclerosis, are poorly defined biochemically. Few markers (most notably Islet-1 and L-type calcium channels1,2) are known for these cells. Identification of genes uniquely expressed or significantly up-regulated in motor neurons is difficult given the lack of a tissue source that represents these cells exclusively. A motor neuron rich source of tissue, spinal cord (without sensory ganglia) and a motor neuron poor tissue source, posterior cerebral cortex compared by means of suppression subtractive hybridization represents a solution to this problem.
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