Generation of transgenic golden Syrian hamsters

Abstract

Golden Syrian hamsters are small rodents, but they display many features that resemble the physiology and metabolism of humans. [7], all of which are not observed in other rodents such as mice and rats. Consequently, hamsters, like humans, exhibit enhanced susceptibility to atherosclerosis (AS) and diabetes [8], which led to the widespread use of hamsters in studies on AS and diabetes.In the past 2-3 decades, due to the fast development of transgenic and knockout mice, hamsters were gradually replaced by these mouse models. However, due to multiple differences between mice and humans with respect to physiology and metabolism, the use of genemanipulated mice has limited value in disease modeling and pathophysiological studies. Extensive literature search has revealed an absence of reports on genetically manipulated hamster models. To capitalize on the special metabolic features of hamsters, we aim to generate genemanipulated hamsters as an alternate rodent model for general applications. As the initial step to create a genetically manipulated hamster, we utilized a highly efficient lentiviral vector to generate transgenic hamsters expressing enhanced green fluorescent protein (eGFP).By modifying and optimizing the protocols for producing transgenic mice and rabbits in our laboratory [9, 10], we developed a specific procedure for hamster superovulation, fertilized egg harvesting, perivitelline space microinjection and embryo transfer. After the successful culture of fertilized hamster eggs that developed into 4-and 8-cell embryos in vitro ( Figure 1A), we implanted these embryos into pseudopregnant females. We obtained 7-10 pups/litter in 4 out of 7 surrogate mothers. Next, we microinjected 50-100 picoliters of a lentiviral

Reduced high density lipoprotein cholesterol in severe hypertriglyceridemic ApoCIII transgenic mice via lowered hepatic ApoAI synthesis

“…All of these characters are not observed in mice. Therefore, other animal models, such as hamster [30]whose lipid profile is much more similar with human, should be used to further investigate the relationship between ApoCIII and HDL metabolism in our future study.…”

Mapping the Specific Amino Acid Residues That Make Hamster DPP4 Functional as a Receptor for Middle East Respiratory Syndrome Coronavirus

“…Descriptions of transgenic hamsters are virtually absent from the scientific literature due to the absence of specific gene-targeting tools. Utilization of the clustered regularly interspaced short palindromic repeat (CRISPR)/ Cas9 system would allow efficient gene targeting and the generation of a new small-animal model (9,10). Hamster a hpi, hours postinfection; boldface, human residues; italics, hamster residues; ϩ/ϩ, viral growth; ϩ/Ϫ, attenuated viral growth; Ϫ/Ϫ, no viral growth; ϽDL, below the detection limit of the assay.…”

“…Therefore, if a treatment against MERS-CoV is shown to be successful in the mouse model, further characterization of the treatment needs to be performed in NHPs, a relatively expensive animal model to which access is limited. The availability of a second small-animal model (such as hamsters with a modified DPP4 [9,10]) to confirm results obtained with the mouse model would ensure that only treatments with a high likelihood of succeeding would be investigated in NHPs.Fourteen amino acids are important in the interaction between blades IV and V of human DPP4 (hDPP4) and the receptor binding domain (RBD) of the MERS-CoV spike protein (11,12). We previously showed that hamster DPP4 (haDPP4) does not function as a receptor for MERS-CoV.…”

“…Therefore, if a treatment against MERS-CoV is shown to be successful in the mouse model, further characterization of the treatment needs to be performed in NHPs, a relatively expensive animal model to which access is limited. The availability of a second small-animal model (such as hamsters with a modified DPP4 [9,10]) to confirm results obtained with the mouse model would ensure that only treatments with a high likelihood of succeeding would be investigated in NHPs.…”

Experimental Models in Syrian Golden Hamster Replicate Human Acute Pancreatitis

“…They display many features that resemble humans in physiology, such as diet reactivity, metabolism, and infection of pathogenic microorganisms123. Recently, the application of genetic manipulation of embryonic cells in hamster made a success of generating transgenic or knockout hamster models45. Because of these combined features animal models for human metabolic diseases can be promisingly built on hamster in many cases instead of mice or rats in the future.…”