The hormonal action of IGF1 in postnatal mouse growth

Elias Stratikopoulos, Matthias Szabolcs, Ioannis Dragatsis, Apostolos Klinakis, Argiris Efstratiadis

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

The mammalian insulin-like growth factor 1 (IGF1), which is a member of a major growth-promoting signaling system, is produced by many tissues and functions throughout embryonic and postnatal development in an autocrine/paracrine fashion. In addition to this local action, IGF1 secreted by the liver and circulating in the plasma presumably acts systemically as a classical hormone. However, an endocrine role of IGF1 in growth control was disputed on the basis of the results of a conditional, liver-specific Igf1 gene knockout in mice, which reduced significantly the level of serum IGF1, but did not affect average body weight. Because alternate interpretations of these negative data were tenable, we addressed genetically the question of hormonal IGF1 action by using a positive experimental strategy based on the features of the cre/loxP recombination system. Thus, we generated bitransgenic mice carrying in an Igf1 null background a dormant Igf1 cDNA placed downstream of a transcriptional "stop" DNA sequence flanked by loxP sites (floxed) and also a cre transgene driven by a liver-specific promoter. The Igf1 cDNA, which was inserted by knock-in into the mutated and inactive Igf1 locus itself to ensure proper transcriptional regulation, was conditionally expressed from cognate promoters exclusively in the liver after Cre-mediated excision of the floxed block. Our genetic study demonstrated that the endocrine IGF1 plays a very significant role in mouse growth, as its action contributes approximately 30% of the adult body size and sustains postnatal development, including the reproductive functions of both mouse sexes.

Original languageEnglish (US)
Pages (from-to)19378-19383
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number49
DOIs
StatePublished - Dec 9 2008

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Somatomedins
Growth
Liver
Complementary DNA
Gene Knockout Techniques
Body Size
Transgenes
Knockout Mice
Genetic Recombination
Embryonic Development
Body Weight
Hormones
Serum

All Science Journal Classification (ASJC) codes

  • General

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The hormonal action of IGF1 in postnatal mouse growth. / Stratikopoulos, Elias; Szabolcs, Matthias; Dragatsis, Ioannis; Klinakis, Apostolos; Efstratiadis, Argiris.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 49, 09.12.2008, p. 19378-19383.

Research output: Contribution to journalArticle

Stratikopoulos, Elias ; Szabolcs, Matthias ; Dragatsis, Ioannis ; Klinakis, Apostolos ; Efstratiadis, Argiris. / The hormonal action of IGF1 in postnatal mouse growth. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 49. pp. 19378-19383.
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