The Applicability of Mouse Models to the Study of Human Disease

Abstract

The laboratory mouse Mus musculus has long been used as a model organism to test hypotheses and treatments related to understanding the mechanisms of disease in humans; however, for these experiments to be relevant, it is important to know the complex ways in which mice are similar to humans and, crucially, the ways in which they differ. In this chapter, an in-depth analysis of these similarities and differences is provided to allow researchers to use mouse models of human disease and primary cells derived from these animal models under the most appropriate and meaningful conditions. Although there are considerable differences between mice and humans, particularly regarding genetics, physiology, and immunology, a more thorough understanding of these differences and their effects on the function of the whole organism will provide deeper insights into relevant disease mechanisms and potential drug targets for further clinical investigation. Using specific examples of mouse models of human lung disease, i.e., asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis, this chapter explores the most salient features of mouse models of human disease and provides a full assessment of the advantages and limitations of these models, focusing on the relevance of disease induction and their ability to replicate critical features of human disease pathophysiology and response to treatment. The chapter concludes with a discussion on the future of using mice in medical research with regard to ethical and technological considerations.

Animal Models Reflecting Chronic Obstructive Pulmonary Disease and Related Respiratory Disorders: Translating Pre-Clinical Data into Clinical Relevance

“…Although elastase involvement in COPD has been shown, the direct instillation of elastases into an animal model offers little understanding of disease pathogenesis [175]. The model reduces the impact of immune cell involvement, a vital aspect in human COPD pathophysiology, and instead induces "artificial" tissue destruction [176,177]. These models may be more relevant for the initial assessment of alveolar damage mechanisms.…”

“…The disadvantages to using CS exposure include the resistance of some species, such as mice, to CSinduced neutrophilic inflammation and damage, which ceases after CS exposure is discontinued [176,195]. As such, many have commented that the murine model of CS exposure fails to capture clinical disease complexities [177].…”

“…Mice offer several advantages over other species, including low housing costs, relatively short breeding time in comparison to higher species, extensive knowledge of the genome [224,225], ease of genetic modifications [160,226], and heterogeneity of reactions to exogenous stimuli amongst different murine strains [177,224,227]. CS is most commonly used to induce COPD in mice [25,176,195,[228][229][230].…”

“…It is important to note lung anatomical differences between humans and mice, with the latter possessing fewer submucosal glands and only six to eight pre-bronchioles before termination, with further anatomical differences reported elsewhere [177,233]. Importantly for respiratory studies, humans inhale smoke through the mouth predominantly, whilst mice are obligate nose-breathers [234].…”

CRISPR-Cas systems: Overview, innovations and applications in human disease research and gene therapy

“…Among numerous model animals, mice are widely used for scientific studies and recognized as the most important model animals in human disease research [83] . So far, researchers have successfully generated many genetically modified mouse models, such as cancer, cardiovascular disease, cardiomyopathy, Huntington's disease, albino, deafness, hemophilia B, obesity, urea cycle disorder and muscular dystrophy [84] , [85] , [86] , [87] , [88] , [89] , [90] , [91] , [92] , [93] .…”