Journal of Physiology and Biochemistry

, Volume 70, Issue 1, pp 129–139

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

  • I. Castilla-Cortazar
  • L. Guerra
  • J. E. Puche
  • U. Muñoz
  • R. Barhoum
  • E. Escudero
  • J. L. Lavandera
Original Paper

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.

Keywords

IGF-1 IGF-1 receptor GH receptor Liver cirrhosis Laron syndrome GH/IGF-1 axis IGF-1 deficiency IGFBP-3 Gene expression Aging 

Abbreviations

Bw

Body weight

Cat

Catalase

CO

Control group (wild-type mice)

ELISA

Enzyme-linked immunosorbent assay

Gclc

Glutamate–cysteine ligase catalytic subunit

GH

Growth hormone

GHR

Growth hormone receptor

Hspa1b

Heat shock protein 1B

Hz

Heterozygous

IGF-1

Insulin-like growth factor-1

IGF-1R

IGF-1 receptor

IGFBP

Insulin-like growth factor binding protein

KO

Knockout

Neo

Neomicine

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Copyright information

© University of Navarra 2013

Authors and Affiliations

  • I. Castilla-Cortazar
    • 1
    • 2
  • L. Guerra
    • 1
  • J. E. Puche
    • 1
  • U. Muñoz
    • 1
  • R. Barhoum
    • 1
  • E. Escudero
    • 1
  • J. L. Lavandera
    • 1
  1. 1.Institute of Applied Molecular Medicine (IMMA), Department of Medical Physiology, School of MedicineUniversidad CEU San PabloMadridSpain
  2. 2.School of MedicineUniversidad CEU San PabloMadridSpain

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