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IGF-I is required for normal embryonic growth in mice
L Powell-Braxton1, P Hollingshead, C Warburton
1Department of Endocrine Research, Genentech, Inc., South San Francisco, California 94080-4990.
Genes & Development
|December 1, 1993
Summary
Insulin-like Growth Factor-I (IGF-I) is crucial for embryonic development. Mice lacking functional IGF-I genes exhibit severe growth deficits and high perinatal mortality, underscoring its essential role.
Area of Science:
- Developmental Biology
- Endocrinology
- Genetics
Background:
- Insulin-like Growth Factor-I (IGF-I) is a hormone influencing growth, metabolism, and homeostasis.
- While IGF-I is known for postnatal effects, its embryonic role is less understood compared to IGF-II.
Purpose of the Study:
- To investigate the essential role of IGF-I in normal embryonic development using a genetically modified mouse model.
Main Methods:
- Homologous recombination in embryonic stem (ES) cells was used to generate mice with an inactive IGF-I gene.
- Phenotypic analysis of heterozygous and homozygous mutant mice, including growth measurements and histopathology.
Main Results:
- Heterozygous IGF-I mutant mice were 10-20% smaller with reduced organ, muscle, and bone mass but normal histology.
- Homozygous IGF-I mutant mice (IGF-I-/-) were <60% of wild-type birth weight, with >95% perinatal mortality.
- Histopathology revealed underdeveloped muscle tissue and disorganized lung structures in homozygous mutants.
Conclusions:
- IGF-I is essential for normal embryonic development in mice.
- The absence of IGF-I leads to severe growth retardation, organ underdevelopment, and high perinatal lethality.