An impending crisis in the provision of histopathology expertise for mouse functional genomics

Abstract

The generation of new mouse models of human disease is accelerating rapidly, due to the completion of whole-genome sequencing efforts and technological advances in the manipulation of the mouse genome. We sought to investigate manpower issues in the provision of histopathology expertise for mouse functional genomics and compared this to the perceived demand from principal investigators (PIs). Through the European Commission (EC)-funded PRIME pathology training initiative, two questionnaires were devised to collect information from pathologists and EC-funded PIs on the current provision of mouse histopathology expertise in Europe and the demands for this service. We find that pathological analysis is being performed almost exclusively by professionally qualified pathologists, generally employed in clinical diagnostic posts, where the work is undertaken as collaboration outside of their contractual commitments but without previous training in veterinary or comparative pathology. The results indicate that there is a lack of both trainees and provision of specialist training in this field. Unsurprisingly, the availability of diagnostic expertise and advice falls far short of the number of genetically engineered mice (GEM) being generated for analysis. We analyse these results with reference to previous studies and discuss solutions for the future recruitment, training and funding for pathologists in mouse functional genomics in Europe.

Integrating pathology into human disease modelling – how to eat the elephant

“…Contrary to what has often been suggested (Warren et al, 2009), there might not be an actual lack of mouse pathology expertise globally, but rather a lack of available posts in academia for mouse pathologists. There are many toxicological pathologists (1200 in the US alone, 145 in US academia) (Turner et al, 2014), all of whom, already having experience of mouse histology, genetically modified mice and common background pathology, should be competent to analyse mouse tissues.…”

“…The usefulness of pathology in the study of human disease using mouse models has been repeatedly extolled in recent years; however, there have been parallel warnings of an apparent lack of available resources in this area (Warren et al, 2009). A new study by Hibret Adissu and colleagues from the University of Toronto in collaboration with researchers involved in the Sanger Mouse Genetics Project highlights the value of pathology in confirming the results of in vivo phenotyping tests and identifying additional phenotypes not revealed in high-throughput mouse phenotyping pipelines such as the International Mouse Phenotyping Consortium (IMPC) (Adissu et al, 2014).…”

Pathology of the Laboratory Mouse

“…All of the countries represented agreed that although there remains a shortage of pathologists (DVM or MD) or trainees with laboratory mouse expertise (Schofield et al 2009), the current number of pathologists in the major centers, augmented by development of online data-sharing tools for image sharing and annotation between distributed experts, would make full pathology analysis feasible, at least for the expected caseload from the IMPC project. A major disincentive to young pathologists to specialize in genetically engineered mice (GEMs) is the lack of a viable career path in academia (Sundberg et al 2004; Warren et al 2009) or basic biomedical research, in part because of the increasing difficulty of obtaining research funds, even in established university positions, with junior pathologists opting instead for the more traditional and well-paid careers in industry (mainly in safety assessment toxicology and research). Lack of trainee awareness of academic/biomedical research-based career opportunities poses additional problems for recruitment.…”

Do we see what we think we see? The complexities of morphological assessment

“…This is one of the elegant aspects of using virtual microscopy and decision mapping for developing virtual training environments in pathology and simulating diagnostic procedures. Virtual microscopy itself is now being used more widely in education and testing in pathology 40–43, and also potentially allows us to fill major gaps in pathology expertise such as in mouse histopathology, where there is a rapidly expanding requirement for expertise and not enough trainees in this field 44.…”