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

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

J D Coffin et al. Mol Biol Cell. 1995 Dec.

Free PMC article

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.

PubMed Disclaimer

Similar articles

• Three forms of rat basic fibroblast growth factor are made from a single mRNA and localize to the nucleus.
  Powell PP, Klagsbrun M. Powell PP, et al. J Cell Physiol. 1991 Aug;148(2):202-10. doi: 10.1002/jcp.1041480204. J Cell Physiol. 1991. PMID: 1880150
• A new 34-kilodalton isoform of human fibroblast growth factor 2 is cap dependently synthesized by using a non-AUG start codon and behaves as a survival factor.
  Arnaud E, Touriol C, Boutonnet C, Gensac MC, Vagner S, Prats H, Prats AC. Arnaud E, et al. Mol Cell Biol. 1999 Jan;19(1):505-14. doi: 10.1128/MCB.19.1.505. Mol Cell Biol. 1999. PMID: 9858574 Free PMC article.
• Translation of CUG- but not AUG-initiated forms of human fibroblast growth factor 2 is activated in transformed and stressed cells.
  Vagner S, Touriol C, Galy B, Audigier S, Gensac MC, Amalric F, Bayard F, Prats H, Prats AC. Vagner S, et al. J Cell Biol. 1996 Dec;135(5):1391-402. doi: 10.1083/jcb.135.5.1391. J Cell Biol. 1996. PMID: 8947560 Free PMC article.
• Basic fibroblast growth factor (FGF-2): the high molecular weight forms come of age.
  Yu PJ, Ferrari G, Galloway AC, Mignatti P, Pintucci G. Yu PJ, et al. J Cell Biochem. 2007 Apr 1;100(5):1100-8. doi: 10.1002/jcb.21116. J Cell Biochem. 2007. PMID: 17131363 Review.
• IRES-dependent regulation of FGF-2 mRNA translation in pathophysiological conditions in the mouse.
  Gonzalez-Herrera IG, Prado-Lourenco L, Teshima-Kondo S, Kondo K, Cabon F, Arnal JF, Bayard F, Prats AC. Gonzalez-Herrera IG, et al. Biochem Soc Trans. 2006 Feb;34(Pt 1):17-21. doi: 10.1042/BST20060017. Biochem Soc Trans. 2006. PMID: 16246170 Review.

Cited by

• The Potential of FGF-2 in Craniofacial Bone Tissue Engineering: A Review.
  Novais A, Chatzopoulou E, Chaussain C, Gorin C. Novais A, et al. Cells. 2021 Apr 17;10(4):932. doi: 10.3390/cells10040932. Cells. 2021. PMID: 33920587 Free PMC article. Review.
• FGFRL1 and FGF genes are associated with height, hypertension, and osteoporosis.
  Cho HW, Jin HS, Eom YB. Cho HW, et al. PLoS One. 2022 Aug 18;17(8):e0273237. doi: 10.1371/journal.pone.0273237. eCollection 2022. PLoS One. 2022. PMID: 35980984 Free PMC article.
• FGF-2 suppresses expression of nephronectin via JNK and PI3K pathways.
  Kato T, Yamada A, Ikehata M, Yoshida Y, Sasa K, Morimura N, Sakashita A, Iijima T, Chikazu D, Ogata H, Kamijo R. Kato T, et al. FEBS Open Bio. 2018 Apr 19;8(5):836-842. doi: 10.1002/2211-5463.12421. eCollection 2018 May. FEBS Open Bio. 2018. PMID: 29744297 Free PMC article.
• Genomic expression analysis of rat chromosome 4 for skeletal traits at femoral neck.
  Alam I, Sun Q, Liu L, Koller DL, Liu Y, Edenberg HJ, Econs MJ, Foroud T, Turner CH. Alam I, et al. Physiol Genomics. 2008 Oct 8;35(2):191-6. doi: 10.1152/physiolgenomics.90237.2008. Epub 2008 Aug 26. Physiol Genomics. 2008. PMID: 18728226 Free PMC article.
• FGF signaling inhibits chondrocyte proliferation and regulates bone development through the STAT-1 pathway.
  Sahni M, Ambrosetti DC, Mansukhani A, Gertner R, Levy D, Basilico C. Sahni M, et al. Genes Dev. 1999 Jun 1;13(11):1361-6. doi: 10.1101/gad.13.11.1361. Genes Dev. 1999. PMID: 10364154 Free PMC article.

References

1. 1. Cell. 1994 Jul 29;78(2):335-42 - PubMed
2. 1. Dev Biol. 1994 Jul;164(1):123-32 - PubMed
3. 1. Nat Genet. 1994 Sep;8(1):98-103 - PubMed
4. 1. Mol Reprod Dev. 1994 Sep;39(1):69-81; discusison 81-2 - PubMed
5. 1. Mol Reprod Dev. 1994 Sep;39(1):90-100; discussion 100-1 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Atypon
  • Europe PubMed Central
  • PubMed Central

• Other Literature Sources

  • The Lens - Patent Citations Database

• Molecular Biology Databases

  • Mouse Genome Informatics (MGI)