roles. GEM may involve a single gene and attempt to mimic the human genetic disorder, or GEM may represent non‐familial genetic changes in the pathways to disease including cancer. Tumor frequency data in wild‐type control mice, especially in aging studies, have often been reported in various strains and stocks [1, 7, 23, 35, 37, 38]. While these reports provide general background information on the frequency of cancer types in a wildtype inbred strain, the actual frequency will vary based on substrain, husbandry, and other factors, necessitating the use of adequate numbers of control mice for studies on frequency of cancers in GEMs.
Immunohistochemistry (IHC), Scoring, Image Analysis, and Other Supportive Research Pathology Techniques
A variety of special pathology techniques are important adjuncts to mouse research. These include immunohistochemistry (IHC), in situ hybridization (ISH), ultrastructure, imaging, image analysis, artificial intelligence, machine learning, and a variety of molecular techniques. Most chapters will include examples of these for the various tissues. Some publications offer reviews of the use of IHC in mice [39–42] and Internet sites offer IHC protocols (http://tumor.informatics.jax.org/mtbwi/index.do, https://www.niehs.nih.gov/research/resources/protocols/protocols‐immuno/index.cfm) and whole slide images (http://tumor.informatics.jax.org/mtbwi/lymphomaPathology.jsp).
Histopathology scoring (grading) of lesion type and severity can often be used for mouse models of disease, genetics, and preclinical development for drugs [6, 34,43–45]. Examples are given in some chapters. The newer fields of image analysis, artificial intelligence, and machine learning are growing quickly [46, 47] and allow scientific analysis of quantitative pathology data.
Publication of Erroneous Pathology Data: Inadvertent Fraud?
Publications involving mice and other animals sometimes include histopathology figures that do not show what is described in the figure legend and/or text [2, 48, 49]. This problem has occurred most often in publications that do not appear to include a pathologist as a co‐author, and in journals that are not pathology‐based. The absence of pathology support at a research institution may be due to cost, lack of pathology staff, and/or the desire of a scientist and his staff to attempt pathology on their own (“Do It yourself pathology”) [50]. These publications containing clearly erroneous findings may be due to lack of pathologists as reviewers of the submitted manuscript and/or a lack of the journal reviewers and editors who understand the value of accurate histopathology description and interpretation. Emails to authors and editors involved with the publication usually evoke no responses, and rarely concern even if there is a response. The only solution is for scientists and journals to understand the importance of pathology as a critically important medical specialty as part of doing research using mice.
Overall Organization of the Book
The Pathology of Genetically‐engineered Mice (GEM) and Other Mutant Mice is organized into introductory chapters on concepts on the use of mice in biomedical research and the critical need to include mouse pathology expertise. The mouse pathology chapters, by organ system or other topics, are generally organized into sections on anatomy and histology, special necropsy organ protocols, aging/spontaneous strain specific lesions, GEM, and references. The reference listings are not an extensive review of the topic since there are thousands of such references, but they do include recent reviews and relevant classic and current publications. Tables and figures call attention to important information on the mice and their applications.
Acknowledgments
The editors wish to thank the lead and co‐authors of all chapters for their valuable contributions and interactions with the editors.
This work was supported grants from the National Institutes of Health (R01‐CA089713 and P30‐CA034196 to JPS).
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