Engineering Large Animal Species to Model Human Diseases

Abstract

Animal models are an important resource for studying human diseases. Genetically engineered mice are the most commonly used species and have made significant contributions to our understanding of basic biology, disease mechanisms, and drug development. However, they often fail to recreate important aspects of human diseases and thus can have limited utility as translational research tools. Developing disease models in species more similar to humans may provide a better setting in which to study disease pathogenesis and test new treatments. This unit provides an overview of the history of genetically engineered large animals and the techniques that have made their development possible. Factors to consider when planning a large animal model, including choice of species, type of modification and methodology, characterization, production methods, and regulatory compliance are also covered.

Sheep as a large animal model for cochlear implantation

“…While large animals can be disadvantageous in terms of housing or managing, they are more similar to humans in terms of anatomic dimensions and physiology. 5 Large animals like sheep may also be appropriate to be a model of hearing loss given the anatomical and physiological similarities to the human cochlea. Cordero et al 6 described sheep ears as a potentially good animal model for stapedectomy training due to relatively low overall costs, easy access to the stapes, and anatomic similarities to human.…”

Building Blood Vessel Chips with Enhanced Physiological Relevance

“…[15] In contrast, small animal-based models exhibit notable genetic and cellular differences from human physiology, which may lead to biased results regarding disease pathogenesis and therapeutic effects. [16,17] Furthermore, tissue chips can precisely control and decouple multiple experimental factors, beneficial for exploiting the inherently complex human physiology, in contrast to other in vitro models, such as Petri dish-based ones, which are focused on maintaining cell proliferation in vitro. Thus, tissue chips, as a viable alternative to other tissue/disease-modeling approaches, are promising for in vitro recapitulation of the sophisticated human physiology and pathology at the tissue and organ level and are expected to transform the landscapes of fundamental biological research, [18][19][20] drug screening and toxicology, [21][22][23][24] and possibly, clinical trials.…”

Application of the transgenic pig model in biomedical research: A review

“…Furthermore, it has high similarity in physiological, biochemical, and developmental processes. In addition, the availability of embryonic stem cell (ESC) lines highlighted mice’s significance in animal model usage ( Bronson and Smithies, 1994 ; Rogers, 2016b ; a ). This is why mouse models can intimate drug functions when a disease occurs in them.…”