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Mouse models of IGF-I deficiency generated by gene targeting
C Warburton1, L Powell-Braxton
1Genentech Inc., South San Francisco, CA 94080, USA.
Summary
Insulin-like growth factor-I (IGF-I) is a crucial hormone for growth. Gene targeting in mice revealed IGF-I
Area of Science:
- Endocrinology and Molecular Biology
- Genetics and Genomics
- Developmental Biology
Background:
- Insulin-like growth factor-I (IGF-I) is a homologous hormone to insulin, mediating growth hormone's anabolic effects.
- IGF-I and IGF-II are key growth factors, with IGF-II predominantly expressed in fetal development.
- IGF-I interacts with the type 1 receptor, while IGF-II utilizes both type 1 and type 2 receptors.
Purpose of the Study:
- To investigate the function of IGF-I in whole animal development.
- To understand the specific roles of IGF-I during pre- and postnatal growth phases.
Main Methods:
- Utilizing homologous recombination to generate mouse strains with targeted IGF-I deficiency.
- Employing genome manipulation techniques for functional gene analysis in vivo.
Main Results:
- Mice deficient in IGF-I production exhibited significant developmental abnormalities.
- The study demonstrated critical roles for IGF-I in both prenatal and postnatal development.
Conclusions:
- IGF-I is essential for normal mammalian development, impacting both fetal and post-hatching growth.
- Genome manipulation in mice provides a powerful tool for dissecting complex gene functions in vivo.