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by Sharon Ricks, technical writer, NIDDK

May 11 was moving day for 11 NIDDK researchers and 400 miceout of their friendly but modest quarters in the upper reaches of the Clinical Center and into the new NIDDK Laboratory of Genetics and Physiology (LGP).

The new lab spans rooms 101 through 115 of Building 8 and boasts a new laser-capture microscope (see "Hot Methods: Laser Capture Microdissection," NIH Catalyst, November­December, 1997, page 12) and new video imaging equipment. It officially opened June 11, replacing the developmental biology section of the Laboratory of Biochemistry and Metabolism.

The lab explores genetic switches and biochemical pathways that control normal and oncogenic mammary gland developmentand it's a tribute to 16 years of study of mammary gland development and physiology. (Though the lab is dedicated to the study of the mammary gland, other projects, such as the study of germ-cell development in the testes, are also on the agenda.)

The research originated in the quest of a graduate student in Cologne, Germany, who was working on his thesis project in the genetics lab in which the lysozyme gene, a relative of the milk protein, a-lactalbumin, had been cloned. The student wanted to isolate the a-lactalbumin gene in the mouse to identify the gene's structure and to determine whether the structure and functional domain were conserved through evolution. Instead, he discovered what would prove to be a powerful new research tool.

Lothar Hennighausen and the fruits of his new lab: a laser-capture view of mammary gland mysteries

"I did not manage to isolate the a-lactalbumin gene," says the chief of the new NIDDK lab, Lothar Hennighausen, reminiscing on his early work. "It tricked us. We were surprised to find that the milk protein is expressed 100-fold less in the mammary tissue of mice than in that of all other species. Instead, I isolated for the first time mammary-specific genes for the mouse, including a novel gene called the whey acidic protein (Wap)."

When Hennig-hausen came to the NIDDK Laboratory of Biochemistry and Metabolism in 1985, he picked up the research again and discovered that the Wap gene was almost exclusively expressed in mammary tissue and that its control switches targeted other genes to mammary tissue for expression in transgenic animals. The new promoter could therefore be used to target oncogenes to mammary epithelial cells and to create mouse models of human breast cancer, Hennighausen recalls. It could also be applied to the creation of "mammary bioreactors" to express pharmaceuticals in the milk of transgenic mice and livestock, such as are now used commercially to produce blood-clotting factors in sheep and goats.

These days, says Kay-Uwe Wagner, a postdoc in the lab, "we are doing tissue-specific gene knockouts," linking the Wap gene with an enzyme specific for whatever gene is slated for removal from the mammary gland, such as the bcl-X gene, and determining its culpability in tumorogenesis. The lab is also creating technologies to deregulate gene expression at specific times during development.

Lothar Hennighausen (seated), encircled by labmates (left to right): Ulrike Wagner, Svetlana Stegalkina, Kay-Uwe Wagner, Patricia Dierisseau, Justin McShane, Ed Rucker, Nataly Strunnikova, Robin Humphreys, Jonathan Shillingford, Gertraud Robinson, Annie Guerrero, and Marta Gallego.

To Hennighausen, the mammary gland harbors fundamental lessons of how organs are built. "In the virgin gland you just see ducts, and as soon as pregnancy sets in, the gland takes off," he observes, noting that many rounds of cell proliferation and differentiation lead to an organ designed to produce large amounts of milk. "After weaning," he adds, "the gland completely regresses, and in a short time, 99 percent of the epithelial cells die." He says the lab will explore the signals that trigger cell death for clues on how to destroy tumors.

NIDDK Scientific Director Allen Spiegel says Hennighausen's work has illuminated the role of several hormones, growth factors, and their signal-transduction pathways in the complex changes that occur in the breast during normal pubertal development, pregnancy, lactation, and involution, as well as in the neoplastic process that leads to breast cancer.

Colleagues at NCI are quite interested in the work of the LGP. "Lothar's lab is working to identify all the genes that are expressed during normal mammary gland development and to define when they're expressed," says Bob Callahan, chief of the Oncogenetics Section in NCI's Laboratory of Tumor Immunology and Biology. "His is probably the only lab doing that for any particular tissue," Callahan says, "and it provides a basis for understanding where things go wrong during mammary tumorgenesis."

NCI supports two related Web sites: NIDDK's Mammary Gland Anatomy Project at <http://mammary.nih.gov/mgap > and the Biology of the Mammary Gland at <http://mammary.nih.gov >, both of which are managed by Hennighausen and supported by CIT's Jai Evans.

NIDCD: Ten Years!
Friday, October 2, 1998, 10:30 a.m., Natcher Conference Center, NIH.

Celebrate the decade's research in human communication with the NIH and NIDCD directors and other speakers.

For more info, call 496-7243 or 402-0252 (TTY); for agenda and luncheon reservation form, visit


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