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

Abstract

Mouse models are increasingly being used for the study of human disease, and the generation and functional characterisation of new models is underpinned by high-throughput phenotyping consortia such as the International Mouse Phenotyping Consortium. A new study by Adissu and colleagues, published in Disease Models & Mechanisms, demonstrates the usefulness of histopathology in providing corroborative information and uncovering novel phenotypes in genetically modified mice in a high-throughput screen. Although pathology is recognised as a valuable tool to enhance our understanding of animal disease models, it has also been systematically under-resourced. This Editorial aims to highlight ways in which the gap between the usefulness of pathology and its perceived inaccessibility can be addressed by considering pragmatic solutions for planning, resourcing and accessing pathology expertise. The role of funding agencies, academic centres and journals in ensuring that the value of pathology is fully recognised and is adequately supported and funded is also discussed.

Principles and approaches for reproducible scoring of tissue stains in research

“…One study reported that nearly a third of IHC slides evaluated by an external quality assessment program did not give a staining result that was satisfactory for analysis [5]. Reproducible immunostaining requires optimized and standardized tissue protocols to ensure consistent and reproducible results [13,14,27,28]. A study by Engel and Moore [18] identified more than 60 variables in the pre-analytical stage alone, beginning with proper sample collection and handling and including multiple aspects of fixation, processing, embedding, slide drying, and storage.…”

“…); chromogen (3,3′-diaminobenzidine (DAB), etc. ); and type of counterstain [5,7,10,13,14,16,20,24,25,27,28,36]. An additional challenge is nonspecific cross-reactivity, the binding of the antibody to an epitope different from the directed target (off-target structure) [37,38].…”

On the Organization of a Drug Discovery Platform

“…"Exploring" means several things in this context, from exploring the disease to exploring the tools and the literature to validate a target. The literature is rather scarce in this context, but one resource is the essay by Scudamore, who tries to make us understand how difficult and diverse this area could be [3].…”

The Vital Role of Pathology in Improving Reproducibility and Translational Relevance of Aging Studies in Rodents

“…This is for financial and logistical reasons as well as a perceived lack of access to expertise or failure to realize that histopathology contributes meaningfully to an understanding of treatment intervention effects. 2,41,64,65 The powerful multi-disciplinary datasets generated in preclinical testing are obtained through in-life and terminal metrics, consensus terminology and diagnostic criteria, lesion scoring, and data management. 32,33,64,65 Protocols and experimental designs should be standardized and well described.…”

“…2,41,64,65 The powerful multi-disciplinary datasets generated in preclinical testing are obtained through in-life and terminal metrics, consensus terminology and diagnostic criteria, lesion scoring, and data management. 32,33,64,65 Protocols and experimental designs should be standardized and well described. 8,15,52,58,67,35 Data must be appropriately collected, assessed, and interpreted by experienced professionals with formal pathology training who understand the limitations of the study design, model, and types of data sets.…”