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

J. D. Coffin, R. Z. Florkiewicz, J. Neumann, T. Mort-Hopkins, G. W. Dorn, P. Lightfoot, R. German, P. N. Howles, A. Kier, B. A. O'Toole, J. Sasse, A. M. Gonzalez, A. Baird, T. Doetschman

Research output: Contribution to journalArticlepeer-review

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
StatePublished - 1995
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

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