Abnormal bone growth and selective translational regulation in basic fibroblast growth factor (FGF-2) transgenic mice

J. Douglas Coffin, Robert Z. Florkiewicz, John Neumann, Tracy Mort-Hopkins, Gerald W. Dorn, Paula Lightfoot, Rebecca German, Philip N. Howles, Ann Kier, Barbara A. O'Toole, Joachim Sasse, Ana Maria Gonzalez, Andrew Baird, Thomas Doetschman

Research output: Contribution to journalArticle

243 Scopus citations

Abstract

Basic fibroblast growth factor (FGF-2) is a pleiotropic growth factor detected in many different cells and tissues. Normally synthesized at low levels, FGF-2 is elevated in various pathologies, most notably in cancer and injury repair. To investigate the effects of elevated FGF-2, the human full- length cDNA was expressed in transgenic mice under control of a phosphoglycerate kinase promoter. Overexpression of FGF-2 caused a variety of skeletal malformations including shortening and flattening of long bones and moderate macrocephaly. Comparison by Western blot of FGF-2 transgenic mice to nontransgenic littermates showed expression of human FGF-2 protein in all major organs and tissues examined including brain, heart, lung, liver, kidney, spleen, and skeletal muscle; however, different molar ratios of FGF- 2 protein isoforms were observed between different organs and tissues. Some tissues preferentially synthesize larger isoforms of FGF-2 while other tissues produce predominantly smaller 18-kDa FGF-2. Translation of the high molecular weight isoforms initiates from unconventional CUG codons and translation of the 18-kDa isoform initiates from an AUG codon in the FGF-2 mRNA. Thus the Western blot data from the FGF-2 transgenic mice suggest that tissue-specific expression of FGF-2 isoforms is regulated translationally.

Original languageEnglish (US)
Pages (from-to)1861-1873
Number of pages13
JournalMolecular biology of the cell
Volume6
Issue number12
DOIs
StatePublished - Dec 1995
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Coffin, J. D., Florkiewicz, R. Z., Neumann, J., Mort-Hopkins, T., Dorn, G. W., Lightfoot, P., German, R., Howles, P. N., Kier, A., O'Toole, B. A., Sasse, J., Gonzalez, A. M., Baird, A., & Doetschman, T. (1995). Abnormal bone growth and selective translational regulation in basic fibroblast growth factor (FGF-2) transgenic mice. Molecular biology of the cell, 6(12), 1861-1873. https://doi.org/10.1091/mbc.6.12.1861