University builds a mouse house

By Roger Segelken

They will never replace the Big Red Bear mascots, but little mice of varied colors and genetic makeups are becoming symbols of life sciences research progress at Cornell.

Studies employing transgenic mice ­ those with added genes from other species as well as the so-called knockout mice with certain genes deleted ­ have been underway at Cornell on a limited basis. Soon, researchers will have an on-campus source of made-to-order mice from the university's first specific-pathogen-free mouse facility to genetically transform and breed the most-used animal model in biomedical research.

The Core Transgenic Mouse Facility, a 12,000-square-foot core center for transgenic mice, is scheduled to open in the spring. In the new facility, located in the College of Veterinary Medicine, Michael Kotlikoff, left, chair of the Department of Biomedical Sciences, pulls a mouse out of a cage for viewing, assisted by Ke-Yu Deng, director of transgenic services. Alexis Wenski-Roberts/College of Veterinary Medicine

Located in the College of Veterinary Medicine, the 12,000-square-foot core "mouse house" will serve satellite mouse facilities around campus. In total, $6.2 million, all from a single gift, is being spent on building, upgrading and outfitting transgenic mouse facilities in existing buildings, including the Biotechnology Building and the Department of Human Ecology. The second phase of the program, which will include a facility in the proposed life sciences technology building, is budgeted at $15 million.

Mice are a highly regarded asset in research, according to Michael Kotlikoff, professor of biomedical sciences in the veterinary college and director of the Cornell Core Transgenic Mouse Facility, because they are the single species in which the full range of genetic manipulations are currently available and can be used to efficiently determine mammalian gene function. "Mice are an important tool in the effort to understand genetic factors that underlie diseases, such as cancer and obesity; to determine the function of individual genes in mammals, including humans, and to better understand complex traits and physiological processes," Kotlikoff explained.

In addition to Kotlikoff's laboratory, numerous investigators across campus will take advantage of the new facility. Additionally, as part of Cornell's Genomics Initiative, departments in the colleges of Veterinary Medicine, Arts and Sciences and Agriculture and Life Sciences are recruiting faculty who require transgenic mouse facilities. Estimates suggest that within five years more than 40 faculty members at Cornell will be significant users of the Cornell Core Transgenic Facility.

Kotlikoff also stresses the importance of these facilities in providing the most up-to-date undergraduate, graduate and professional training in biology.

"Gain-of-function" transgenic mice are produced by microinjecting fertilized mouse eggs with a "transgene," an artificial gene cloned in the laboratory by recombinant DNA technology. "Loss-of-function" or knockout mice are produced by genetically altering an embyronic stem cell in the laboratory and then injecting that cell into a developing embryo early in its development. The eggs or embryos are transferred to a foster mother for gestation. Soon after birth, the young animals are genetically screened to determine which are truly transgenic ­ that is, those in which the desired genes are expressed and are likely to be transmitted to subsequent generations of mice. It is critical for many faculty research programs to have the capability to produce genetically altered mice at Cornell ­ commercial facilities are expensive and slow, requiring long quarantine times before mice can be used in research.

The university's new veterinary college core mouse facility is expected to house up to 30,000 mice. "That may sound like a lot, but a single researcher using mice intensively in his or her research can require 2,000 or 3,000 animals," Kotlikoff said.

The core mouse house will be operated as a barrier facility to keep disease pathogens away from the mice, not because the animals have diseases they could transmit to humans, the director emphasized. "The spread of infectious disease, such as mouse viruses, in mouse colonies is a particular problem," he said. Specially designed mechanical and air-handling systems ­ as well as a quarantine requirement for animals shipped to campus ­ will keep the mice isolated from disease. Even individual mouse cages, which are cleaned in high-capacity, cage-washing machines and sterilized in special autoclaves, have their own micro-ventilation systems.

The Core Transgenic Mouse Facility is scheduled to open in the spring, with Ke-Yu Deng serving as the director of transgenic services. But already the presence of mice is attracting humans. Within the next year, at least six researchers in specialties such as murine pathology and functional genomics will join the faculty.