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

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-len...

Full description

Saved in:
Bibliographic Details
Published in:Molecular biology of the cell 1995-12, Vol.6 (12), p.1861-1873
Main Authors: Coffin, J D, Florkiewicz, R Z, Neumann, J, Mort-Hopkins, T, Dorn, 2nd, G W, Lightfoot, P, German, R, Howles, P N, Kier, A, O'Toole, B A
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Blotting, Western
Bone and Bones - abnormalities
Bone and Bones - pathology
Bone Development
DNA Primers
DNA, Complementary
Fibroblast Growth Factor 2 - biosynthesis
Fibroblast Growth Factor 2 - genetics
Fibroblast Growth Factor 2 - physiology
Gene Expression
Gene Expression Regulation
Humans
Mice
Mice, Inbred Strains
Mice, Transgenic
Molecular Sequence Data
Organ Specificity
Phosphoglycerate Kinase - genetics
Polymerase Chain Reaction
Promoter Regions, Genetic
Protein Biosynthesis
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.6.12.1861