Pathology of Genetically Engineered and Other Mutant Mice. Группа авторов

      Noah's Arkive was developed in the early 1980s as The International Veterinary Pathology Slide Bank to serve as a repository of slides (2 × 2 color transparencies) contributed by individuals and institutions worldwide. In 1986, this slide archive was made available in a digitized format, on laser videodisks. In 2010, Noah's Arkive was launched as a single web‐based resource. Images cover a broad variety of species not just laboratory mice. As such, it is a powerful resource for comparing lesions between species when working up a new mouse model. When looking up lists of images (7 February 2020), searching just for mouse, there were 141 pages with 100 entries (often with more than one image per entry) per page listed.

Organ/Disease Specific Resources

      Most websites are generic providing examples of lesions or models that cover a broad range of topics and organ systems. However, most investigators focus on a particular disease or group of diseases or specific anatomic sites. Several organ/disease specific websites are listed below that remain active and are maintained at the time of this writing. These sites come and go so one is best advised to do a search under the disease or organ of interest. Many of the disease sites one finds are for patient advocacy groups (foundations) that often provide both patient information and sometimes a review or relevant research that may involve mouse models. While a useful source of information for experts in the field, these resources do not often provide detail on non‐human animal models as they are aimed more at support of the clinical practice and medical research communities. Other sites have been developed by investigators working with specific models or fine‐tuning discoveries in the many large‐scale mutant producing programs. Several are provided below.

      Bone Diseases: Skeletal Phenotyping of IMPC/KOMP Mice (http://www.bonebase.org)

      The Knockout Mouse Program (KOMP) is a United States initiative in collaboration with the International Knockout Mouse Consortium (IKMC) to generate a large number of laboratory mice with a single gene inactivated (null mouse) eventually for all protein coding genes, one at a time. A collaboration between investigators at several institutions have been systematically analyzing bones in C57BL/6NJ mice generated by KOMP. This is not one of the primary sites generating and phenotyping these mutant mice, but rather a group specializing in detailed analysis of subtle abnormalities only of bones. The group is focused on screening gene knockout mice for variation in bone mass using μCT and histomorphometry to systematically analyze mice generated from the various KOMP primary sites [68].

      Skin Diseases: Skinbase (http://eulep.pdn.cam.ac.uk/~skinbase/index.php)

      While there initially was a group that systematically reviewed skin, hair, and nails in KOMP mice [53, 69], this was discontinued. Some examples of skin phenotypes in mice with spontaneous single gene mutations are available as whole slide scans on Skinbase, a subdirectory of Pathbase (http://www.pathbase.net). This site also has labeled images of normal skin, hair follicles, and nails to explain normal anatomy of these structures. Pathbase itself has thousands of tiff files on normal and abnormal examples in mice from wild type inbred strains to spontaneous single gene mutations in mice, to mutations caused by a variety of man‐made methods (radiation, chemical mutagenesis, and genetically engineered mice).

      GenitoUrinary Development Molecular Anatomy Project (GUDMAP) (https://www.gudmap.org)

      GenitoUrinary Development Molecular Anatomy Project (GUDMAP) is a consortium of laboratories working to provide the scientific and medical community with tools to facilitate research on the GenitoUrinary (GU) tract. This resource is effectively a toolkit for the study of the mammalian urogenital system with a great deal of information on mouse mutants, tools, and strains. It presents a very significant educational resource for urogenital and prostate development, together with a collection of immunohistochemical, histological, and immunofluorescence images, and gene expression data for the mouse GU tract [70].

      Mouse Brain Atlas (https://developingmouse.brain‐map.org, https://mouse.brain‐map.org)

      The mouse brain atlas is part of the Allen Brain Atlas project (https://portal.brain‐map.org) and presents high‐resolution physical atlases of the adult and embryonic mouse brains based on histological sections annotated to gene expression at cellular resolution. The atlas has an interactive viewer with annotations based on a high‐resolution ontology for brain anatomy. There is also an atlas of the mouse spinal cord with an expression color map and serial histological sections. This is a powerful set of tools for the anatomy and molecular anatomy of the mouse brain and, for example, allows users to search for different anatomic regions with similar patterns of gene expression. There is related single cell data on morphology, gene expression, and single cell electrophysiology together with access to electrophysiological models. These data are all accessible through an API as well as a web interface [71].

      Atlas of Mouse Cardiovascular Development (https://www.devbio.pitt.edu/research/atlas‐mouse‐cardiovascular‐development)

      This site presents a developmental atlas of the mouse cardiovascular system using episcopic fluorescence image capture (EFIC) imaging from E9.5 to term. Embryo sections are available in multiple orientations and can be viewed using a fly‐through interactive viewer. Some examples of EFIC 3D reconstructions are provided showing a variety of congenital cardiovascular anomalies seen in several knockout and ENU‐induced mouse mutants [72, 73].

      Mouse/Human Disease Phenotype Databases

The connection between a mouse model and a corresponding human disease can be difficult to identify. MGI has multiple resources that allow for the identification of human disease models. MGD has the Human–Mouse: Disease Connection (HMDC) that enables searches for potential mouse models, candidate genes, and similarity between mouse models and human patients. Gene entries in MGD have links to predicted vertebrate orthologs in other species databases including Homologene, HGNC, OMIM, and Entrez Gene. MMHC contain tumor phenotypes from potential human disease models including human corresponding examples.

      Online Mendelian Inheritance in Man (OMIM) (https://www.ncbi.nlm.nih.gov/omim)

      OMIM is a comprehensive database on human genes and genetic disorders and has been publicly available since 1987 [74]. OMIM is continually updated from the public literature and has links to other species databases. OMIM is the internet version of the multivolume book titled Mendelian Inheritance in Man by Victor McCusik [75] and is based at Johns Hopkins University. OMIM entries are classified using a standardized system of MIM numbers (denoting genetic classifications) and OMIM disorder codes (indicating loci associated genetic based diseases). OMIM concentrates on the genotype/phenotype relationship. OMIM entries contain text summaries of associated clinical features, molecular genetics, references, clinical synopses, phenotypic series the entry belongs to, and multiple graphic representations of the data [74]. Information and references on various animal models, including those in mice, that mimic or are confirmed orthologs is provided.

      Emouseatlas (https://www.emouseatlas.org/emap/home.html)

      The Emouseatlas focuses on embryonic development of the laboratory mouse [76–81]. This website has four modules.