Minireview: tissue-specific versus generalized gene targeting of the igf1 and igf1r genes and their roles in insulin-like growth factor physiology.
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.
Butler
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The Vollum Institute, Oregon Health Sciences University, Portland, Oregon 97201, USA.
LeRoith
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D
D000818:Animals; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000502:physiology*
D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D017526:Receptor, IGF Type 1