title: A preliminary report on spinal muscular atrophy lymphoblastoid cell lines: are they an appropriate tool for drug screening?
abstract: BACKGROUND
  Spinal muscular atrophy (SMA) is a neurodegenerative disease of the motor neurons that results in progressive muscle weakness. It is also the leading hereditary cause of infant mortality. Homozygous loss of the survival motor neuron (SMN1) gene causes SMA, and the number of copies of the SMN2 gene modulates the severity of the disease. Increasing the expression of the SMN2 gene by pharmacological agents is one of the therapeutic approaches currently being implemented.
  
  
  METHODS
  In this preliminary study, we investigated the effect of phenylbutyrate, a histone deacetylase (HDAC) inhibitor, on SMN2 expression in two SMA type III Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines to understand the suitability of lymphoblastoid cell lines in drug screening. These cell lines are regarded as a good source as they can easily be established from the peripheral leucocytes of patients. Quantitative analysis of SMN2 mRNA was performed on established cell lines treated with various concentrations of phenylbutyrate and for a range of incubation periods using real-time polymerase chain reaction. Western blot analysis was used to determine SMN protein levels.
  
  
  RESULTS
  Real-time polymerase chain reaction and Western blot analysis demonstrated that the levels of SMN2 full-length (fl-SMN2) transcripts and protein were not increased in phenylbutyrate-treated cell lines compared to non-treated controls.
  
  
  CONCLUSIONS
  These results suggest that EBV-transformed lymphoblastoid cell lines are not suitable for studying the effect of certain HDAC inhibitors on SMN2 gene expression.
authors.affiliation: Department of Medical Biology, Hacettepe University, Faculty of Medicine, Ankara, Turkey. didayan@hacettepe.edu.tr
authors.forename: Didem
authors.initials: D
authors.lastname: Dayangaç-Erden
authors.forename: Haluk
authors.initials: H
authors.lastname: Topaloğlu
authors.forename: Hayat
authors.initials: H
authors.lastname: Erdem-Yurter
mesh_terms: D000328:Adult; D002461:Cell Line, Transformed; D002648:Child; D004353:Drug Evaluation, Preclinical; D004854:Herpesvirus 4, Human; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010654:Phenylbutyrates / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D055532:SMN Complex Proteins / Q000096:biosynthesis / Q000235:genetics; D014897:Spinal Muscular Atrophies of Childhood / Q000473:pathology*; D055540:Survival of Motor Neuron 2 Protein
chemical_list: D056572:Histone Deacetylase Inhibitors; D010654:Phenylbutyrates; D012333:RNA, Messenger; D055532:SMN Complex Proteins; C526477:SMN2 protein, human; D055540:Survival of Motor Neuron 2 Protein