Abstract
Phenotypic analysis of genetically engineered mice and detailed evaluations of mouse models of disease have become increasingly important areas of expertise for the veterinary pathologist. Over the last few years, several articles, editorials, and letters have appeared in journals and in the news media, emphasizing the common theme of “one medicine —one pathology.” These articles highlight a few key observations: 1) pathologists are the “gatekeepers of translational research,” 2) mice represent 90% or more of the animals used in National Institutes of Health (NIH)–funded research, 3) there is an acute shortage of mouse pathologists in biomedical research, and 4) the lack of pathology support has, on occasion, led to erroneous interpretations that have been published in scientific journals.1–8, 10, 12 Unfortunately, while veterinary pathology residents leave training programs well prepared for diagnostic pathology, it appears that most residents get only limited, if any, exposure to either routine or unusual lesions unique to mice. In support of this observation, unpublished data derived from the Veterinary Student and Resident Forum, a forum held at the American College of Veterinary Pathologists' (ACVP) meeting for veterinary students interested in pathology residencies, revealed that 67% of the responding programs stated that <5% of their total caseload was composed of laboratory animals. Thus it can be assumed that these trainees have minimal exposure to mice despite the fact that mice are used far more often in biomedical research than any other animals.11
In the fall of 2007, a small, informal group of members of the ACVP began discussing the unique challenges facing veterinary pathologists who provide research pathology support in medical schools or research institutions. These pathologists are often the sole veterinary pathologist, and the majority of the casework involves experimental mouse pathology and genetically engineered mice. These mouse models often display complex or unique pathologic alterations, which are often compounded by experimental studies. A networking system of “mouse pathologists” would be a valuable resource for those of us currently in such positions—hence the formation of “The Mouse Pathologists' Consortium” (MPC). The goal of this group was to formalize the loose network of mouse pathologists into a supportive community that could serve as a resource for those working in the research diagnostic environment. With this consortium, the foundation has been placed to promote the dissemination of information and the education of present and future mouse pathologists. At present, the group has over 50 members not only from research academics but also from veterinary schools and industry. This collegial interaction has resulted in a close common interest group and established a useful Web-based “Mouse Portal” (restricted access) where information and announcements, as well as images of classic, new, and unusual lesions, can be posted and shared. In addition to strengthening collegial connections, the MPC also provides a forum to discuss the urgent need for more comparative/mouse pathologists in biomedical research and thus the origination of this correspondence.
Traditionally, the only “mouse pathology” training that most current mouse pathologists received came from working with mouse models while pursuing a PhD, attending the C. L. Davis Foundation's Pathology of Laboratory Animals course, short courses at The Jackson Labs, or workshops on phenotypic analysis of genetically engineered mice. However, with the exponential expansion of genetically engineered mouse populations around the globe, the growing need for veterinary pathologists who are skilled in the nuances of mouse pathology would be better served with more formal, more extensive training. Many of these pathologists currently working in medical schools or research institutes may not have the infrastructure, manpower, or adequately diverse caseload necessary to oversee a comprehensive anatomic or clinical pathology residency training program. However, they are well positioned to mentor “senior residents,” board-eligible pathologists, or newly certified pathologists in what we propose to call “Mouse Pathobiology Fellowships.” These fellowships would allow participants to be exposed to comprehensive mouse pathobiology through hands-on training and supervised interactions with investigators in diverse biomedical disciplines. Together with the use of currently available resources (e.g., commercial courses, on-line databases) this training format could provide a focused, comprehensive education. Individuals completing a mouse pathobiology fellowship would be valuable assets in the biomedical/academic community and would be experienced collaborators in settings where the “team approach” to biomedical research is emphasized.
The MPC is proposing a basic curriculum that could serve as a guideline for any institution wishing to establish a fellowship, while realizing that this curriculum will likely vary according to the strengths of each institution and the duration of the fellowship (ideally for 1 full year). Briefly, important concepts to incorporate into such a curriculum should include but not be limited to:
Basic mouse biology and pathology: relevant history of the research mouse, strain origins, mouse nomenclature; gross and microscopic anatomy/comparative approach to humans; murine infectious diseases; common strain-associated pathology; husbandry/breeding-related pathology; embryology, etc.
Experimental pathology and associated “tools of the trade”: tumor classification/standardization; approaches for phenotypic characterization of genetically engineered mice (GEM); advanced histology techniques; and pathology associated with commonly employed experimental techniques, etc.
Familiarity with commonly used research techniques: in vivo imaging, microarrays, tissue arrays, laser-capture microscopy; techniques involved in the generation of GEM; in vivo evaluations of behavior, cognition, memory, cardiovascular and respiratory function, metabolism; interactions with scientists for consultation on experimental design, proper controls, collection and fixation of target tissues, etc.
In addition to such a curriculum, the education of a mouse pathobiology fellow would be enhanced by participation in established courses and related activities such as The Jackson Laboratory Annual Workshop on the Pathology of Mouse Models for Human Disease, Charles River Short Course on Laboratory Animal Science, and The Johns Hopkins' Phenotyping Symposium; access to on-line courses such as offered through the University of California at Davis and the Center for Genomic Pathology (http://ctrgenpath.net/); monthly pathology rounds with other institutions via Aperio or the Mouse Portal; and access to and utilization of online databases.9
The successful implementation of such fellowships, regardless of the tremendous need to provide more skilled mouse/comparative pathologists, is ultimately dependent on monetary resources. But who will pay for such a focused subset of pathology training, particularly given our current economic climate? A select few institutions, in realizing that a fellowship of this kind could ultimately benefit their own programs, may decide to allocate the funding. More likely, however, academic institutions will have to partner with pharmaceutical and biotech companies, who are already generously sponsoring many positions in traditional residency training programs, and discussions are currently under way with the ACVP/STP Coalition on ways to increase mouse pathobiology training. While the NIH awards various training grants that promote veterinarians in research (T32, T35, K01, K08, etc.), these funding opportunities are aimed at training individuals for careers as independent researchers, not at training comparative pathologists who play such vital roles as collaborators in biomedical research.
The dilemma continues, but the concept of yearlong mouse pathobiology fellowships is one that demands further consideration. Implementation of such fellowships could serve as a mechanism to help fill the void of pathologists experienced in experimental, mouse, and comparative pathology.