Overexpression of ovine insulin-like growth factor-I (IGF-I) in the mammary glands of transgenic mice
Evidence indicates that the mammary gland may contribute to its own development by the production of insulin-like growth factor-I (IGF-I). To generate a model for investigation of the effects of enhanced IGF-I synthesis in the mammary gland, six transgenic founder mice were produced by microinjection of a cDNA sequence encoding ovine IGF-I (oIGF-I) under the control of the glucocorticoid-responsive mouse mammary tumor virus (MMTV) promoter. Transgenic lines were established from each MMTV-IGF-I transgenic founder, and four virgin and four lactating mice from each transgenic line were analyzed for transgene expression following administration of dexamethasone or vehicle. Virgin mice from three transgenic lines (15, 26, and 29) expressed oIGF-I mRNA and recombinant IGF-I in the mammary gland, although stimulation with exogenous dexamethasone was required for expression. Lactating mice from four transgenic lines (2, 15, 26, and 29) expressed oIGF-I mRNA in mammary tissue, but only three of those lines (15, 26, and 29) produced detectable recombinant IGF-I in milk and mammary tissue. Recombinant IGF-I was not detected in plasma from any of the transgenic lines. The biological activity of recombinant IGF-I secreted into the milk of lactating transgenic mice was demonstrated in vitro by stimulation of ([³H]thymidine incorporation into DNA of immortalized bovine mammary epithelial cells. The MMTV-IGF-I transgenic mice will provide a model for evaluating the effects of increased mammary synthesis of IGF-I on mammary gland development and function.