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Minireview: Tissue-Specific Versus Generalized Gene Targeting of the igf1 and igf1r Genes and Their Roles in Insulin-Like Growth Factor Physiology

The Vollum Institute (A.A.B.), Oregon Health Sciences University, Portland, Oregon 97201, Clinical Endocrinology Branch (D.L.), NIDDK, National Institutes of Health, Bethesda, Maryland 20892-1758

Address all correspondence and requests for reprints to: Derek LeRoith, National Instututes of Health 3, NIH MSC 1758, Building 10, Room 8D12, 10 Center Drive, Bethesda, Maryland 20892-1758. E-mail: derek{at}helix.nih.gov

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.