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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #155195
Title: GENETIC MANIPULATION OF MAMMARY GLAND DEVELOPMENT AND LACTATION

Author
item HADSELL, DARRYL - BAYLOR COLL OF MEDICINE

Submitted to: International Society for Research on Human Milk and Lactation
Publication Type: Book / Chapter
Publication Acceptance Date: 10/1/2003
Publication Date: 10/1/2003
Citation: HADSELL, D.L. 2003. GENETIC MANIPULATION OF MAMMARY GLAND DEVELOPMENT AND LACTATION. INTERNATIONAL SOCIETY FOR RESEARCH ON HUMAN MILK AND LACTATION. In: Pickering, L.K., Morrow, A.L., Schanler, R.J., Ruiz-Palacios, G.M., editors. Advances in Experimental Medicine and Biology. Kluwer Publishers. p. 229-251.

Interpretive Summary: Interpretive Summary not needed for this 115.

Technical Abstract: The mammalian genome is now believed to contain some 30,000 to 40,000 different genes. Of these an estimated 42% have no function is known. Genetically engineered mouse models (GEMM) have been a powerful tool available for determining gene function in vivo. In the mammary gland, a variety of genetic engineering approaches have been successfully applied to understanding the importance of specific gene products to mammary gland development and lactation. Our own laboratory has applied genetically engineered mice to understanding the regulation of mammary gland development and lactation by insulin-like growth factors (IGF) and by the transcription factor, upstream stimulatory factor (USF-2). Our studies on transgenic mice that over express IGF-I have demonstrated the importance IGF-dependent signaling pathways to maintenance of mammary epithelial cells during the declining phase of lactation. Our analysis of early developmental processes in mammary tissue from mice which carry a targeted mutation in the IGF-I receptor gene suggests that IGF-dependent stimulation of cell cycle progression is more important to early mammary gland development than potential anti-apoptotic effects. Lastly, our studies on mice, that carry a targeted mutation of the Usf2 gene, have demonstrated that this gene is necessary for normal lactation and have highlighted the importance of this gene to maintenance of protein synthesis. These studies, as well as those of others, have highlighted both the strengths and limitations inherent in the use of GEMM. These limitations serve as the driving force behind the development of new experimental strategies and genetic engineering schemes which will allow for a full understanding of gene function within the mammary gland.