PUBLICATION

Muscle-specific growth hormone receptor (GHR) overexpression induces hyperplasia but not hypertrophy in transgenic zebrafish

Authors
Figueiredo, M.A., Mareco, E.A., Silva, M.D., and Marins, L.F.
ID
ZDB-PUB-110901-11
Date
2012
Source
Transgenic Research   21(3): 457-469 (Journal)
Registered Authors
Figueiredo, Marcio de Azevedo, Marins, Luis Fernando
Keywords
transgenic zebrafish, growth hormone receptor, insulin-like growth factor I, suppressors of cytokine signaling, hyperplasia, skeletal muscle
MeSH Terms
  • Animals
  • Animals, Genetically Modified/genetics
  • Animals, Genetically Modified/metabolism
  • Body Weight
  • Gene Expression Regulation, Developmental*
  • Gene Transfer Techniques
  • Hyperplasia/genetics
  • Hyperplasia/metabolism
  • Hypertrophy/genetics
  • Hypertrophy/metabolism
  • Luminescent Proteins/metabolism
  • Models, Animal
  • Muscle, Skeletal/metabolism
  • Muscle, Skeletal/pathology*
  • Myogenic Regulatory Factors/genetics
  • Myogenic Regulatory Factors/metabolism
  • Promoter Regions, Genetic
  • Receptor, IGF Type 1/genetics
  • Receptor, IGF Type 1/metabolism
  • Receptors, Somatotropin/genetics
  • Receptors, Somatotropin/metabolism*
  • Signal Transduction
  • Suppressor of Cytokine Signaling Proteins/genetics
  • Suppressor of Cytokine Signaling Proteins/metabolism
  • Zebrafish/genetics
  • Zebrafish/growth & development
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
21863247 Full text @ Transgenic. Res.
Abstract
Even though growth hormone (GH) transgenesis has demonstrated potential for improved growth of commercially important species, the hormone excess may result in undesired collateral effects. In this context, the aim of this work was to develop a new model of transgenic zebrafish (Danio rerio) characterized by a muscle-specific overexpression of the GH receptor (GHR) gene, evaluating the effect of transgenesis on growth, muscle structure and expression of growth-related genes. In on line of transgenic zebrafish overexpressing GHR in skeletal muscle, no significant difference in total weight in comparison to non-transgenics was observed. This can be explained by a significant reduction in expression of somatotrophic axis-related genes, in special insulin-like growth factor I (IGF-I). In the same sense, a significant increase in expression of the suppressors of cytokine signaling 1 and 3 (SOCS) was encountered in transgenics. Surprisingly, expression of genes coding for the main myogenic regulatory factors (MRFs) was higher in transgenic than non-transgenic zebrafish. Genes coding for muscle proteins did not follow the MRFs profile, showing a significant decrease in their expression. These results were corroborated by the histological analysis, where a hyperplasic muscle growth was observed in transgenics. In conclusion, our results demonstrated that GHR overexpression does not induce hypertrophic muscle growth in transgenic zebrafish probably because of SOCS impairment of the GHR/IGF-I pathway, culminating in IGF-I and muscle proteins decrease. Therefore, it seems that hypertrophy and hyperplasia follow two different routes for entire muscle growth, both of them triggered by GHR activation, but regulated by different mechanisms.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping