IGF-I is required for normal embryonic growth in mice

• Published in: Genes & development 1993-12, Vol.7 (12B), p.2609-2617
• Main Authors: POWELL-BRAXTON, L, HOLLINGSHEAD, P, WARBURTON, C, DOWD, M, PITTS-MEEK, S, DALTON, D, GILLETT, N, STEWART, T. A
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Biological and medical sciences; Cell Line; Classical genetics, quantitative genetics, hybrids; Embryonic and Fetal Development - physiology; Female; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Insulin-Like Growth Factor I - deficiency; Insulin-Like Growth Factor I - genetics; Insulin-Like Growth Factor I - physiology; Male; Mice - abnormalities; Mice - embryology; Mice - genetics; Mice, Inbred C57BL; Molecular Sequence Data; Phenotype; Pregnancy; Vertebrata
• ISSN: 0890-9369; 1549-5477
• DOI: 10.1101/gad.7.12b.2609

IGF-I is a pleiotropic hormone reported to affect linear growth, glucose metabolism, organ homeostasis, and the immune and neurologic systems. In contrast to IGF-II, IGF-I is expressed at low levels embryonically and has been thought to be more important for postnatal growth and development. To investigate the role of IGF-I in normal development we generated mice with an inactive IGF-I gene by homologous recombination in ES cells. Heterozygous mice are healthy and fertile, but they are 10-20% smaller than wild-type littermates and have lower than normal levels of IGF-I. The size reduction is attributable to a decrease in organs and muscle and bone mass. However, all tissues appear histologically normal. At birth homozygous mutant mice (IGF-I-/-) are < 60% body weight of wild type. Greater than 95% of IGF-I-/- pups die perinatally. Histopathology is characterized by underdevelopment of muscle tissue. Lungs of late embryonic and neonates also appeared less organized with ill-defined alveolae. IGF-I appears to be essential for correct embryonic development in mice.