Training Mouse Pathologists: Five Years of Pathology of Mouse Models of Human Disease Workshops

On September 10–16, 2006 the 5th annual workshop, Pathology of Mouse Models of Human Disease, for human and veterinary pathologists was held at the Fred Hutchinson Cancer Center in Seattle, WA. In this report we outline the rationale for setting up this workshop series, summarize our experience in its development, and outline our main goals and perspectives.

The laboratory mouse has been critical to biomedical research since Clarence Cook Little defied the thoughts of the day nearly a century ago by creating the first inbred mouse strain (1). By the end of the millennium just a few years ago inbred mice, and more importantly, genetically engineered mice (GEMs), became the primary tool (2) for major genetic based biomedical breakthroughs. The development of this tool created a problem that has been evident for decades but brought to a head in recent years; whereas the technology to create mutant mice has become more or less routine, there is a shortage of experts to do the requisite histopathologic phenotyping in which accurate comparisons are made with human diseases. Veterinarians are trained in the pathology of multiple species but have only limited knowledge of human pathology, and their experience with laboratory mice is generally restricted to the diagnosis of infectious disease.

Many veterinary pathologists gain expertise in toxicologic pathology while evaluating rodent tissues for the pharmaceutical industry, but few are trained in the nuances of mouse genetic pathology and the validation of human disease models. Physicians have extensive knowledge of Homo sapiens, but many are not well versed in the intricacies of rodent anatomy and physiology. We have struggled to redefine training programs and services which integrate veterinary and physician pathologists into a cohesive interdisciplinary approach on an institutional basis (3); however, the traditional Hippocratean, mentor-student approach to teaching medicine remains one of the most effective approaches. In 1999, Drs. Jerry Ward and John Sundberg organized the first large meeting to focus on this topic that was held at the National Institutes of Health, called “Pathology of Genetically Engineered Mice.” Although this semicomprehensive meeting resulted in the production of a well-regarded textbook (2), the conference itself was not accessible to many practicing pathologists who needed training and confidence to meet the new demands. Further large meetings, which were held on different continents, eventually evolved into a state of the art program on genetically engineered mice. Problematic was the fact that mouse pathology was no longer the emphasis of this program.

To meet the specific needs of pathologists, we recognized that a different approach was required. In order to encourage direct open interaction and network development, the format was changed to small focused meetings, each of which was led by a core group of veterinary and physician pathologists who enlisted the help of selected world authorities. The annual meetings, each of which featured approximately 15 faculty members, were limited to 20–25 participants on average, and they occurred in different research institutions at locations throughout the United States. The first meeting took place at The Jackson Laboratory in Bar Harbor, Maine on October 8–16, 2002 and subsequent venues included Cornell University, Purdue University, and most recently, the Fred Hutchinson Cancer Center. In 2007, this meeting will return to The Jackson Laboratory to start the cycle again. The goal has been to encourage pathology residents from regional institutions to attend selected lectures, and to encourage investigators to take advantage of the opportunity to interact with the world authorities who visit their campuses. As a consequence of rotating the meeting sites, the involvement of local scientists has provided a diverse and dynamic program.

The basic format has remained the same each year. Each workshop provides a week of intensive training in pathology and histopathology, including didactic sessions in which particular disease areas and models are discussed. The course also provides up to 39 RACE and 39 CME credits that are certified through the AAVSB and Maine Medical Center, respectively. The core faculty are experts in their respective areas of mouse pathology, and they describe the latest breakthroughs in their fields. Additionally, Dr. Matthew H. Kaufman, from the University of Edinbourgh in Scotland, who is well known for his classic texts on mouse embryology (4, 5), introduces this complicated topic each year including the school’s “Mouse Atlas Project” web site 〈http://genex.hgu.mrc.ac.uk/〉. Dr. Xavier Montagutelli, from the Institut Pasteur in Paris, France, covers basic mouse genetics. These and other distinguished scientists provide an international flavor that attracts an intercontinental list of participants to the meeting.

Speakers cover public databases such as The Mouse Genome Informatics Database 〈http://informatics.jax.org/〉; the Mouse Tumor Biology Database 〈http://tumor.informatics.jax.org/〉; Mouse Phenome Database 〈http://phenome.jax.org/〉, Pathbase 〈http://pathbase.net/〉; The NCI Mouse Models of Human Cancer 〈http://emice.nci.nih.gov/〉; and The University of California Comparative Medicine virtual slide site for mouse models of cancer 〈http://imagearchive.compmed.ucdavis.edu/〉. This information provides the participants access to mouse anatomy and pathology resources of which they were often previously unaware. Textbooks that are classics in the field (8–14) are made available. In addition, the organizers contribute to the development of the latest classification systems for mouse proliferative lesions; such classifications have been published in Cancer Research and other top-ranking journals during the past few years.

These annual workshops provide state of the art overview of the pathology of genetically engineered mice. More importantly, they allow for the integration of this field with other research areas such as genetics and molecular biology. Of even greater significance, the workshops promote effective working relationships between veterinary and physician pathologists, in which they join forces to make the most accurate histopathologic interpretations and the most creative uses of these fantastic biomedical tools. Given that the number of applicants consistently exceeds the number of available slots, we look forward to the continuation of these workshops as an important contribution to the research community.