Genetically Engineered Hamster Models of Dyslipidemia and Atherosclerosis.

Abstract

Animal models of human diseases play an extremely important role in biomedical research. Among them, mice are widely used animal models for translational research, especially because of ease of generation of genetically engineered mice. However, because of the great differences in biology between mice and humans, translation of findings to humans remains a major issue. Therefore, the exploration of models with biological and metabolic characteristics closer to those of humans has never stopped.Although pig and nonhuman primates are biologically similar to humans, their genetic engineering is technically difficult, the cost of breeding is high, and the experimental time is long. As a result, the application of these species as model animals, especially genetically engineered model animals, in biomedical research is greatly limited.In terms of lipid metabolism and cardiovascular diseases, hamsters have several characteristics different from rats and mice, but similar to those in humans. The hamster is therefore an ideal animal model for studying lipid metabolism and cardiovascular disease because of its small size and short reproduction period. However, the phenomenon of zygote division, which was unexpectedly blocked during the manipulation of hamster embryos for some unknown reasons, had plagued researchers for decades and no genetically engineered hamsters have therefore been generated as animal models of human diseases for a long time. After solving the problem of in vitro development of hamster zygotes, we successfully prepared enhanced green fluorescent protein (eGFP) transgenic hamsters by microinjection of lentiviral vectors into the zona pellucida space of zygotes. On this basis, we started the development of cardiovascular disease models using the hamster embryo culture system combined with the novel genome editing technique of clustered regularly interspaced short palindromic repeats (CRISPR )/CRISPR associated protein 9 (Cas9). In this chapter, we will introduce some of the genetically engineered hamster models with dyslipidemia and the corresponding characteristics of these models. We hope that the genetically engineered hamster models can be further recognized and complement other genetically engineered animal models such as mice, rats, and rabbits. This will lead to new avenues and pathways for the study of lipid metabolism and its related diseases.