An experimental model of partial insulin-like growth factor-1 deficiency in mice

J Physiol Biochem. 2014 Mar;70(1):129-39. doi: 10.1007/s13105-013-0287-y. Epub 2013 Sep 18.

Abstract

Insulin-like growth factor-1 (IGF-1) is responsible for many systemic growth hormone (GH) functions although it has an extensive number of inherent activities (anabolic, cytoprotective, and anti-inflammatory). The potential options for IGF-1 therapy arise as a promising strategy in a wide list of human diseases. However, deeper studies are needed from a suitable animal model. All human conditions of IGF-1 deficiency consist in partially decreased IGF-1 levels since total absence of this hormone is hardly compatible with life. The aim of this work was to confirm that heterozygous Igf-1 (+/-) mice (Hz) may be considered as an appropriate animal model to study conditions of IGF-1 deficiency, focusing on early ages. Heterozygous Igf-1 (+/-) mice were compared to homozygous Igf-1 (+/+) by assessing gene expression by quantitative PCR, serum circulating levels by ELISA, and tissue staining. Compared to controls, Hz mice (25 days old) showed a partial but significant reduction of IGF-1 circulating levels, correlating with a reduced body weight and diminished serum IGFBP-3 levels. Hz mice presented a significant decrease of IGF-1 gene expression in related organs (liver, bone, testicles, and brain) while IGF-1 receptor showed a normal expression. However, gene expression of growth hormone receptor (GHR) was increased in the liver but reduced in the bone, testicles, and brain. In addition, a significant reduction of cortical bone thickness and histopathological alterations in the testicles were found in Hz mice when compared to controls. Finally, the lifelong evolution of IGF-1 serum levels showed significant differences throughout life until aging in mice. Results in this paper provide evidence for considering heterozygous mice as a suitable experimental model, from early stages, to get more insight into the mechanisms of the beneficial actions induced by IGF-1 replacement therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight
  • Brain / metabolism
  • Brain / pathology
  • Disease Models, Animal
  • Female
  • Femur / pathology
  • Gene Expression
  • Humans
  • Insulin-Like Growth Factor Binding Protein 1 / genetics
  • Insulin-Like Growth Factor Binding Protein 1 / metabolism
  • Insulin-Like Growth Factor Binding Protein 3 / genetics
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism
  • Insulin-Like Growth Factor I / deficiency*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Mice, Transgenic
  • Organ Size
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / metabolism
  • Receptors, Somatotropin / genetics
  • Receptors, Somatotropin / metabolism
  • Testis / metabolism
  • Testis / pathology

Substances

  • Insulin-Like Growth Factor Binding Protein 1
  • Insulin-Like Growth Factor Binding Protein 3
  • Receptors, Somatotropin
  • insulin-like growth factor-1, mouse
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1