Molecular misreading in non-neuronal cells

F.W. van Leeuwen, E.M. Hol, R.W. Hermanussen, M.A.F. Sonnemans, E. Moraal, D.F. Fischer, D.A. Evans, K.F. Chooi, J.P.H. Burbach, D. Murphy

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

+1 Frame-shifted proteins such as amyloid precursor protein(+1) and ubiquitin-B(+1) have been identified in the neuropathological hallmarks of Alzheimer's disease. These frameshifts are caused by dinucleotide deletions in GAGAG motifs of messenger RNA encoded by genes that have maintained the unchanged wild-type DNA sequence. This process is termed 'molecular misreading'. A key question is whether this process is confined to neurons or whether it could also occur in non-neuronal cells. A transgenic mouse line (MV-B) carrying multiple copies of a rat vasopressin minigene as a reporter driven by the MMTV-LTR promotor was used to screen non-neuronal tissues for molecular misreading by means of detection of the rat vasopressin(+1) protein and mutated mRNA. Molecular misreading was demonstrated to occur in several organs (e.g., epididymis and the parotid gland) where transgenic vasopressin expression is abundant, but its penetrance is variable both between and within tissues. This implies that non-neural tissues too, could be affected by cellular derangements caused by molecular misreading.

Original languageEnglish
Pages (from-to)1595-1602
Number of pages8
JournalFASEB Journal
Volume14
Issue number11
Publication statusPublished - Aug 2000

Keywords

  • Animals
  • Cell Line
  • Epididymis
  • Epithelial Cells
  • Frameshifting, Ribosomal
  • Genes, Reporter
  • Immunohistochemistry
  • In Situ Hybridization
  • Male
  • Mice
  • Mice, Transgenic
  • Models, Genetic
  • Mutation
  • Neurons
  • Oligonucleotides, Antisense
  • Parotid Gland
  • Penetrance
  • RNA, Messenger
  • Rats
  • Terminal Repeat Sequences
  • Vasopressins
  • Journal Article
  • Research Support, Non-U.S. Gov't

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