Pathology Principles and Practices for Analysis of Animal Models

Abstract

Over 60% of NIH extramural funding involves animal models, and approximately 80% to 90% of these are mouse models of human disease. It is critical to translational research that animal models are accurately characterized and validated as models of human disease. Pathology analysis, including histopathology, is essential to animal model studies by providing morphologic context to in vivo, molecular, and biochemical data; however, there are many considerations when incorporating pathology endpoints into an animal study. Mice, and in particular genetically modified models, present unique considerations because these modifications are affected by background strain genetics, husbandry, and experimental conditions. Comparative pathologists recognize normal pathobiology and unique phenotypes that animals, including genetically modified models, may present. Beyond pathology, comparative pathologists with research experience offer expertise in animal model development, experimental design, optimal specimen collection and handling, data interpretation, and reporting. Critical pathology considerations in the design and use of translational studies involving animals are discussed, with an emphasis on mouse models.

The Ideal Time for Iron Administration in Anemia Secondary to Blood Loss—An Experimental Animal Model

“…We obtained an iron deficit model associated with anemia by acute blood loss, a feasible experimental method according to the published data [ 21 ]. Specific indications were followed for group allocation [ 22 ], and all the possible variables were reduced to a minimum to respect the general recommendation regarding experimental animal studies [ 23 , 24 ]. This model was sustained by the fact that, in group I, the serum iron was lower than in group 0, the same as for the hemoglobin and ferritin values.…”

Biopharmaceutics 4.0, Advanced Pre-Clinical Development of mRNA-Encoded Monoclonal Antibodies to Immunosuppressed Murine Models

“…Evaluation of alterations caused by novel drugs to the experimental units of a clinical investigation represents the pilar of any safety assessment before applied to human patients. The latter is based on conventional histopathological tests, representing a significant contribution to novel treatment development for both human and animal diseases [63]. We will evaluate malignant alterations to all organs and their corresponding tissues and investigate the causal relationship that might have been developed due to the novel drug treatment exposure and also assess the relevance that the various adverse effect related findings might have for future patients [64].…”

Challenges and Opportunities for the Veterinary Pathologist in Biomedical Research

“…Animal models have been fundamental in preclinical and biomedical research for revealing key biochemical and physiologic processes, clarifying disease mechanisms, and translating biomedical discoveries into effective clinical treatments for human disease. 4,13,43,85,96 Animal models have been critical in the development of history’s most seminal breakthroughs in medicine. For example, insulin was developed in part through the development of multiple surgical and pancreatic extract injection models utilizing dogs, cats, and rabbits.…”

“…In the post genomic era, the term “animal model” evokes images of genetically manipulated mice replicating features of a human disease phenotype, and indeed, US government statistics indicate that approximately 80% to 90% of the animals used in research are mice, rats, and other small rodents. 4,43 Advantages of rodents include relatively low operational costs, extensive genetic information, small size and ease of handling, availability of reagents for molecular techniques, and the existence of models for a plethora of human disease conditions. 4,6,84,85,88 However, now there are a variety of non-rodent model systems available, including rabbits, sheep, pigs, fish, dogs, and nonhuman primates, each offering their own advantages and challenges.…”