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-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.
Coffin
J D
JD
Department of Cell Biology, Scripps Research Institute, La Jolla, CA 92121, USA.
Florkiewicz
R Z
RZ
Neumann
J
J
Mort-Hopkins
T
T
Dorn
G W
GW
Lightfoot
P
P
German
R
R
Howles
P N
PN
Kier
A
A
O'Toole
B A
BA
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D001846:Bone Development; D001842:Bone and Bones / Q000002:abnormalities* / Q000473:pathology; D017931:DNA Primers; D018076:DNA, Complementary; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010735:Phosphoglycerate Kinase / Q000235:genetics; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis
D017931:DNA Primers; D018076:DNA, Complementary; D016222:Fibroblast Growth Factor 2; D010735:Phosphoglycerate Kinase