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 journalArticle

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

Fingerprint

Bone Development
Fibroblast Growth Factor 2
Transgenic Mice
Protein Isoforms
Codon
Western Blotting
Megalencephaly
Phosphoglycerate Kinase
Intercellular Signaling Peptides and Proteins
Skeletal Muscle

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

Cite this

Coffin, J. D., Florkiewicz, R. Z., Neumann, J., Mort-Hopkins, T., Dorn, G. W., Lightfoot, P., ... 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.

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

In: Molecular Biology of the Cell, Vol. 6, No. 12, 1995, p. 1861-1873.

Research output: Contribution to journalArticle

Coffin, JD, Florkiewicz, RZ, Neumann, J, Mort-Hopkins, T, Dorn, GW, Lightfoot, P, German, R, Howles, PN, Kier, A, O'Toole, BA, Sasse, J, Gonzalez, AM, 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, vol. 6, no. 12, pp. 1861-1873.
Coffin JD, Florkiewicz RZ, Neumann J, Mort-Hopkins T, Dorn GW, Lightfoot P et al. Abnormal bone growth and selective translational regulation in basic fibroblast growth factor (FGF-2) transgenic mice. Molecular Biology of the Cell. 1995;6(12):1861-1873.
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. / Abnormal bone growth and selective translational regulation in basic fibroblast growth factor (FGF-2) transgenic mice. In: Molecular Biology of the Cell. 1995 ; Vol. 6, No. 12. pp. 1861-1873.
@article{9d017542352f42e0a3d3e448838dec7e,
title = "Abnormal bone growth and selective translational regulation in basic fibroblast growth factor (FGF-2) transgenic mice",
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.",
author = "Coffin, {J. D.} and Florkiewicz, {R. Z.} and J. Neumann and T. Mort-Hopkins and Dorn, {G. W.} and P. Lightfoot and R. German and Howles, {P. N.} and A. Kier and O'Toole, {B. A.} and J. Sasse and Gonzalez, {A. M.} and A. Baird and T. Doetschman",
year = "1995",
language = "English (US)",
volume = "6",
pages = "1861--1873",
journal = "Molecular Biology of the Cell",
issn = "1059-1524",
publisher = "American Society for Cell Biology",
number = "12",

}

TY - JOUR

T1 - Abnormal bone growth and selective translational regulation in basic fibroblast growth factor (FGF-2) transgenic mice

AU - Coffin, J. D.

AU - Florkiewicz, R. Z.

AU - Neumann, J.

AU - Mort-Hopkins, T.

AU - Dorn, G. W.

AU - Lightfoot, P.

AU - German, R.

AU - Howles, P. N.

AU - Kier, A.

AU - O'Toole, B. A.

AU - Sasse, J.

AU - Gonzalez, A. M.

AU - Baird, A.

AU - Doetschman, T.

PY - 1995

Y1 - 1995

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0028880515&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028880515&partnerID=8YFLogxK

M3 - Article

C2 - 8590811

AN - SCOPUS:0028880515

VL - 6

SP - 1861

EP - 1873

JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

SN - 1059-1524

IS - 12

ER -