title: Identification of a novel transforming growth factor-beta (TGF-beta6) gene in fish: regulation in skeletal muscle by nutritional state.
abstract: BACKGROUND
  The transforming growth factor-beta (TGF-beta) family constitutes of dimeric proteins that regulate the growth, differentiation and metabolism of many cell types, including that of skeletal muscle in mammals. The potential role of TGF-betas in fish muscle growth is not known.
  
  
  RESULTS
  Here we report the molecular characterization, developmental and tissue expression and regulation by nutritional state of a novel TGF-beta gene from a marine fish, the gilthead sea bream Sparus aurata. S. aurata TGF-beta6 is encoded by seven exons 361, 164, 133, 111, 181, 154, and 156 bp in length and is translated into a 420-amino acid peptide. The exons are separated by six introns: >643, 415, 93, 1250, 425 and >287 bp in length. Although the gene organization is most similar to mouse and chicken TGF-beta2, the deduced amino acid sequence represents a novel TGF-beta that is unique to fish that we have named TGF-beta6. The molecule has conserved putative functional residues, including a cleavage motif (RXXR) and nine cysteine residues that are characteristic of TGF-beta. Semi-quantitative analysis of TGF-beta6 expression revealed differential expression in various tissues of adult fish with high levels in skin and muscle, very low levels in liver, and moderate levels in other tissues including brain, eye and pituitary. TGF-beta6 is expressed in larvae on day of hatching and increases as development progresses. A fasting period of five days of juvenile fish resulted in increased levels of TGF-beta6 expression in white skeletal muscle compared to that in fed fish, which was slightly attenuated by one injection of growth hormone.
  
  
  CONCLUSIONS
  Our findings provide valuable insights about genomic information and nutritional regulation of TGF-beta6 which will aid the further investigation of the S. aurata TGF-beta6 gene in association with muscle growth. The finding of a novel TGF-beta6 molecule, unique to fish, will contribute to the understanding of the evolution of the TGF-beta family of cytokines in vertebrates.
authors.affiliation: National Institute of Oceanography, Israel Oceanographic and Limnological Research, Tel Shikmona, POB 8030, Haifa 31080, Israel. bruriaf@gmail.com
authors.forename: Bruria
authors.initials: B
authors.lastname: Funkenstein
authors.forename: Elena
authors.initials: E
authors.lastname: Olekh
authors.forename: Sonia B
authors.initials: SB
authors.lastname: Jakowlew
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D029941:Fish Proteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D007814:Larva / Q000378:metabolism; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism*; D010802:Phylogeny; D021541:Sea Bream / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D016212:Transforming Growth Factor beta / Q000145:classification / Q000235:genetics* / Q000378:metabolism
chemical_list: D029941:Fish Proteins; D016212:Transforming Growth Factor beta
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