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

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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.

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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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Acknowledgments

The authors specially thank Dr. Argiris Efstratiadis for kindly providing the transgenic IGF-1 mice and for his helpful advice. We are also grateful to Ms. Amalia Calderón, Ms. Raquel Romero, and Ms. Susana Arahuetes for their expert secretarial and technical assistance. Special thanks to Dr. Maria Cruz Sádaba and Ms. Elena Ávila for their generous help. This work was supported by the Spanish “I + D Program” SAF 2009–08319.

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Authors and Affiliations

  1. Institute of Applied Molecular Medicine (IMMA), Department of Medical Physiology, School of Medicine, Universidad CEU San Pablo, Madrid, Spain

    I. Castilla-Cortazar, L. Guerra, J. E. Puche, U. Muñoz, R. Barhoum, E. Escudero & J. L. Lavandera

  2. School of Medicine, Universidad CEU San Pablo, Room D-201, C/ Boadilla del Monte s/n, km 5.3, 28668, Madrid, Spain

    I. Castilla-Cortazar

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  1. I. Castilla-Cortazar
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  2. L. Guerra
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Correspondence to I. Castilla-Cortazar.

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Castilla-Cortazar, I., Guerra, L., Puche, J.E. et al. An experimental model of partial insulin-like growth factor-1 deficiency in mice. J Physiol Biochem 70, 129–139 (2014). https://doi.org/10.1007/s13105-013-0287-y

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  • DOI: https://doi.org/10.1007/s13105-013-0287-y

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