Minireview: tissue-specific versus generalized gene targeting of the igf1 and igf1r genes and their roles in insulin-like growth factor physiology

• Published in: Endocrinology (Philadelphia) 2001-05, Vol.142 (5), p.1685-1688
• Main Authors: Butler, A A, LeRoith, D
• Format: Article
• Language: English
• Subjects: Animals; Growth Hormone - secretion; Humans; Insulin-Like Growth Factor I - genetics; Insulin-Like Growth Factor I - physiology; Mice; Mice, Knockout; Organ Specificity; Promoter Regions, Genetic; Receptor, IGF Type 1 - genetics; Receptor, IGF Type 1 - physiology; RNA, Messenger - analysis
• ISSN: 0013-7227
• DOI: 10.1210/en.142.5.1685

The insulin-like growth factors (IGF-I and IGF-II) and the IGF-I receptor are critically important for normal growth and development of the organism. Gene-deletion of these elements has demonstrated that IGF-I is important for both prenatal and postnatal development, whereas IGF-II is important during prenatal stages only. The IGF-I receptor gene-deleted mouse dies at birth apparently as a result of poor muscular development. Utilizing the conditional gene-deletion approach, we have demonstrated that mice lacking the liver IGF-I gene have an approximately 80% reduction in circulating total IGF-I levels. Despite this marked reduction, postnatal growth and development was normal, suggesting that liver IGF-I is not essential for this function. Local tissue IGF-I production was unaffected and may compensate for the lack of the liver IGF-I. Further studies are ongoing to establish the role of the endocrine vs. the autocrine/paracrine IGF-I.