Molecular and functional characterization of two distinct IGF binding protein-6 genes in zebrafish

Wang, X., Lu, L., Li, Y., Li, M., Chen, C., Feng, Q., Zhang, C., and Duan, C.
American journal of physiology. Regulatory, integrative and comparative physiology   296(5): R1348-R1357 (Journal)
Registered Authors
Duan, Cunming, Li, Mingyu
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Brain/embryology
  • Brain/metabolism
  • Cattle
  • Chickens
  • Chromosome Mapping
  • Embryonic Development/genetics
  • Embryonic Development/physiology
  • Heart/embryology
  • Humans
  • Insulin-Like Growth Factor Binding Protein 6/analysis
  • Insulin-Like Growth Factor Binding Protein 6/genetics*
  • Insulin-Like Growth Factor Binding Protein 6/metabolism*
  • Mice
  • Molecular Sequence Data
  • Muscles/embryology
  • Muscles/metabolism
  • Myocardium/metabolism
  • Phylogeny
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Rats
  • Salmon
  • Trout
  • Xenopus
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish/metabolism*
19279291 Full text @ Am. J. Physiol. Regul. Integr. Comp. Physiol.
Insulin-like growth factor binding proteins (IGFBPs) are high affinity binding partners for IGFs and play important roles in growth and development by binding to and modulating IGF activities. In this study, we have identified and characterized two functional IGFBP-6 genes in zebrafish. Structural, phylogenetic, and comparative genomic analyses indicate that they are co-orthologs of the human IGFBP-6 gene. To gain insight into how the duplicated genes may have evolved through partitioning of ancestral functions, gene expression and functional studies were carried out. In adult fish, IGFBP-6a mRNA was most abundantly expressed in the muscle. The levels of IGFBP-6a mRNA in non-muscle tissues were very low or barely detectable. In comparison, the levels of IGFBP-6b mRNA were high in the brain, heart, and muscle, but very low or undetectable in other adult tissues. During embryogenesis, the IGFBP-6a mRNA levels were relatively low. The IGFBP-6b mRNA levels were low during the initial 48 h. They became significantly higher at 72 and 96 hpf. Overexpression of zebrafish IGFBP-6a and -6b caused a similar degree of reduction in body size and developmental rates. No notable effects were observed on cell fate or patterning in these transgenic fish. These data suggest that the duplicated igfbp-6 encodes two functionally equivalent proteins, but they have evolved distinct spatial and temporal expression patterns. These findings are consistent with the notion of an additional gene duplication event in teleost fish and have provided novel insight into the structural and functional evolution of the IGFBP gene family. Key words: Gene duplication, insulin-like growth factor, binding protein, embryo.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes