Pathbase: a new reference resource and database for laboratory mouse pathology

Schofield, Paul N.; Bard, Jonathan; Boniver, Jacques; Covelli, Vincenzo; Delvenne, Philippe; Ellender, M.; Engström, Wilhelm; Goessner, W.; Gruenberger, Michael; Hoefler, Heinz; Hopewell, J. W.; Mancuso, Mariateresa; Mothersill, Carmel; Quintanilla-Martı́nez, Leticia; Rozell, Björn; Sariola, Hannu; Sundberg, John P.; Ward, Andrew

doi:10.1093/rpd/nch101

Cited by 22 publications

(14 citation statements)

References 10 publications

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“…Representative photomicrographs from this and other studies can be accessed on public repositories (Mouse Tumor Biology Database, http://tumor.informatics.jax.org/ and Pathbase, http://www.pathbase.net). 3,33,60,61,63 These data provide a unique resource and background information that can be an aid to correct interpretation of lesions seen in old mice.…”

Section: Introductionmentioning

confidence: 99%

Approaches to Investigating Complex Genetic Traits in a Large-Scale Inbred Mouse Aging Study

et al. 2016

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Inbred mice are a unique model system for studying aging because of the genetic homogeneity within inbred strains, the short life span of mice relative to humans, and the rich array of analytical tools that are available. A large-scale aging study was conducted on 28 inbred strains representing great genetic diversity to determine, using histopathology, the type and diversity of spontaneous diseases aging mice develop. Eighteen inbred strains have had their genomes sequenced and many others have been partially sequenced to provide large repositories of data on genetic variation between the strains. This vast amount of genomic information can be utilized in genome-wide association studies (GWAS) to find candidate genes that are involved in the pathogenesis of spontaneous diseases. We present here, as an illustration, a GWAS of the genetic associations of age-related intestinal amyloidosis which implicates three candidate genes Tram1, Sf3b5, and Stx11. Many of the age-related mouse diseases are similar, if not identical, to human diseases and therefore the genetic discoveries have direct translational benefit. Representative photomicrographs are available on the Mouse Tumor Biology Database and Pathbase to serve as a reference when evaluating inbred mice used in other genetic or experimental studies to rule out strain background lesions.

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Section: Introductionmentioning

confidence: 99%

Approaches to Investigating Complex Genetic Traits in a Large-Scale Inbred Mouse Aging Study

et al. 2016

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“…Anatomical structures were defined using the Mouse Anatomy Ontology (MA) (Hayamizu et al, 2005) and disease diagnoses were entered using the Mouse Pathology ontology (MPATH) (Schofield et al, 2010a; Schofield et al, 2010b). Representative images of lesions in addition to those presented here are available on Pathbase (http://www.pathbase.net/) (Schofield et al, 2004a; Schofield et al, 2004b; Schofield et al 2010b) and in the Mouse Tumor Biology Database (http://tumor.informatics.jax.org/) (Begley et al, 2014; Krupke et al, 2008). …”

Section: Methodsmentioning

confidence: 99%

Genetic determinants of fibro-osseous lesions in aged inbred mice

Berndt

Ackert‐Bicknell

Silva

et al. 2016

Experimental and Molecular Pathology

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Fibro-osseous lesions in mice are progressive aging changes in which the bone marrow is replaced to various degrees by fibrovascular stroma and bony trabeculae in a wide variety of bones. The frequency and severity varied greatly among 28 different inbred mouse stains, predominantly affecting females, ranging from 0% for 10 strains to 100% for KK/HlJ and NZW/LacJ female mice. Few lesions were observed in male mice and for 23 of the strains, no lesions were observed in males for any of the cohorts. There were no significant correlations between strain-specific severities of fibro-osseous lesions and ovarian (r=0.11; P=0.57) or endometrial (r=0.03; P=0.89) cyst formation frequency or abnormalities in parathyroid glands. Frequency of fibro-osseous lesions was most strongly associated (P < 10−6) with genome variations on chromosome (Chr) 8 at 90.6 and 90.8 Mb (rs33108071, rs33500669; P = 5.0 · 10−10, 1.3 · 10−6), Chr 15 at 23.6 and 23.8 Mb (rs32087871, rs45770368; P = 7.3 · 10−7, 2.7 · 10−6), and Chr 19 at 33.2, 33.4, and 33.6 Mb (rs311004232, rs30524929, rs30448815; P=2.8 · 10−6, 2.8 · 10−6, 2.8 · 10−6) in genome-wide association studies (GWAS). The relatively large number of candidate genes identified in the GWAS analyses suggests that this may be an extremely complex polygenic disease. These results indicate that fibro-osseous lesions are surprisingly common in many inbred strains of laboratory mice as they age. While this presents little problem in most studies that utilize young animals, it may complicate aging studies, particularly those focused on bone.

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“…One of many approaches to this problem is to post additional digital images at a variety of magnifications or whole slide images as supplemental data. Images could also be posted on public websites such the Mouse Tumor Biology Database 35, 36 , Gene Expression Database 37 , Pathbase 38, 39 , and many others 5 .…”

Section: Some Examples Of Errors Seen In Reported Histopathological Dmentioning

confidence: 99%

Reproducibility of histopathological findings in experimental pathology of the mouse: a sorry tail

2017

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Reproducibility of in vivo research using the mouse as a model organism depends on many factors including experimental design, strain or stock, experimental protocols, and methods of data evaluation. Gross and histopathology are often the endpoints of such research and there is increasing concern about the accuracy and reproducibility of diagnoses in the literature. In order to reproduce histopathological results, the pathology protocol, including necropsy methods and slide preparation, should be followed by interpretation of the slides by a pathologist familiar with reading mouse slides and familiar with the consensus medical nomenclature used in mouse pathology. Likewise, it is important that pathologists are consulted as reviewers of manuscripts where histopathology is a key part of the investigation. The absence of pathology expertise in planning, executing, and reviewing in vivo research using mice leads to questionable pathology-based findings and conclusions from studies, even in high impact journals. We discuss the various aspects of this problem, give some examples from the literature, and suggest solutions.

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Pathbase: a new reference resource and database for laboratory mouse pathology

Cited by 22 publications

References 10 publications

Approaches to Investigating Complex Genetic Traits in a Large-Scale Inbred Mouse Aging Study

Approaches to Investigating Complex Genetic Traits in a Large-Scale Inbred Mouse Aging Study

Genetic determinants of fibro-osseous lesions in aged inbred mice

Reproducibility of histopathological findings in experimental pathology of the mouse: a sorry tail

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