ZFIN ID: ZDB-PUB-090106-5
Many ribosomal protein mutations are associated with growth impairment and tumor predisposition in zebrafish
Lai, K., Amsterdam, A., Farrington, S., Bronson, R.T., Hopkins, N., and Lees, J.A.
Date: 2009
Source: Developmental dynamics : an official publication of the American Association of Anatomists   238(1): 76-85 (Journal)
Registered Authors: Amsterdam, Adam, Farrington, Sarah, Hopkins, Nancy
Keywords: ribosomal proteins, growth, translation, cancer, zebrafish
MeSH Terms:
  • Animals
  • Chimera/anatomy & histology
  • Chimera/genetics
  • Chimera/growth & development
  • Chimera/metabolism
  • Disease Susceptibility
  • Gene Knockdown Techniques
  • Mutation*
  • Nerve Sheath Neoplasms*/genetics
  • Nerve Sheath Neoplasms*/metabolism
  • Nerve Sheath Neoplasms*/pathology
  • Ribosomal Proteins*/genetics
  • Ribosomal Proteins*/metabolism
  • Zebrafish/anatomy & histology
  • Zebrafish/genetics
  • Zebrafish/growth & development*
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 19097187 Full text @ Dev. Dyn.
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ABSTRACT
We have characterized 28 zebrafish lines with heterozygous mutations in ribosomal protein (rp) genes, and found that 17 of these are prone to develop zebrafish malignant peripheral nerve sheath tumors (zMPNST). Heterozygotes from the vast majority of tumor-prone rp lines were found to be growth-impaired, though not all growth-impaired rp lines were tumor-prone. Significantly, however, the rp lines with the greatest incidence of zMPNSTs all displayed a growth impairment. Furthermore, heterozygous cells from one tumor-prone rp line were out-competed by wild-type cells in chimeric embryos. The growth impairment resulting from heterozygosity for many rp genes suggests that a global defect in protein translation exists in these lines, raising the possibility that a translation defect that precedes tumor development is predictive of tumorigenesis.
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