The History of the WHHL Rabbit, an Animal Model of Familial Hypercholesterolemia (I) - Contribution to the Elucidation of the Pathophysiology of Human Hypercholesterolemia and Coronary Heart Disease -

Shiomi, Masashi

doi:10.5551/jat.rv17038-1

Cited by 13 publications

(11 citation statements)

References 79 publications

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“…In addition, rabbits are the most-used animals for antibody production for biomedical research. Furthermore, rabbits are similar to humans in terms of cardiovascular physiology and lipid metabolism, and they play an important role in studying human diseases such as atherosclerosis and hypercholesterolemia [ 2 , 3 ]. Along with the development of genetic engineering, a number of gene-modified rabbits have been established as experimental models of human diseases.…”

Section: Introductionmentioning

confidence: 99%

Strategies for Highly Efficient Rabbit Sperm Cryopreservation

Nishijima

Kitajima

Matsuhisa

et al. 2021

Animals

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The rabbit is a valuable animal for both the economy and biomedical sciences. Sperm cryopreservation is one of the most efficient ways to preserve rabbit strains because it is easy to collect ejaculate repeatedly from a single male and inseminate artificially into multiple females. During the cooling, freezing and thawing process of sperms, the plasma membrane, cytoplasm and genome structures could be damaged by osmotic stress, cold shock, intracellular ice crystal formation, and excessive production of reactive oxygen species. In this review, we will discuss the progress made during the past years regarding efforts to minimize the cell damage in rabbit sperms, including freezing extender, cryoprotectants, supplements, and procedures.

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Section: Introductionmentioning

confidence: 99%

Strategies for Highly Efficient Rabbit Sperm Cryopreservation

Nishijima

Kitajima

Matsuhisa

et al. 2021

Animals

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“…HCD is currently a common way to establish AS. After HCD treatment for 3 months, plaques will appear in the blood vessels of experimental animals [ 15 , 16 ]. As a small vertebrate, zebrafish has a high degree of similarity with human genes by 87%.…”

Section: Discussionmentioning

confidence: 99%

Zebrafish Model for Screening Antiatherosclerosis Drugs

Han

Zhang

et al. 2021

Oxidative Medicine and Cellular Longevity

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This study is aimed at establishing a zebrafish model of AS, which can be applied for high-throughput screening anti-AS drugs. A zebrafish AS model was induced by high cholesterol diet (HCD) and lipopolysaccharide (LPS). In the early stage of modeling, HCD induced zebrafish to show some early symptoms similar to human AS, mainly cholesterol accumulation, vascular inflammation, lipid metabolism disorder, and oxidative stress. In addition to lipid metabolism disorders, LPS also induced the same symptoms. And when HCD and LPS exist at the same time, these AS symptoms in zebrafish become more severe. When the modeling time reached 45 days, HCD and LPS induce the formation of plaques in zebrafish blood vessels, and these plaques contain fibrous tissue and lipids, which are similar to human AS plaques. We also evaluated the efficacy of some anti-AS drugs (atorvastatin, aspirin, and vitamin C) through these zebrafish AS models. The results found that atorvastatin can significantly reduce the symptoms of AS induced by HCD and LPS, and aspirin and vitamins can significantly reduce the symptoms of AS induced by LPS. It is feasible to use zebrafish to establish an AS model, and the zebrafish AS model can be used for high-throughput screening of anti-AS drugs.

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“…Many atherosclerosis studies have been performed using HcD-fed rabbits (23). Watanabe Heritable Hyperlipidemic (WHHL) rabbits that manifest spontaneous hyperlipidemia, in vivo 35: 2025-2033 (2021) atherosclerosis, and xanthoma of the digital joints are naturally occurring LDLr-mutated rabbit strains and a model of human familial hypercholesterolemia (26,27). WHHL rabbits are widely used for pharmacological and pathological research (27).…”

Section: Discussionmentioning

confidence: 99%

High Pathological Reproducibility of Diet-induced Atherosclerosis in MicrominipigsviaCloning Technology

Otake

Kawaguchi

Enya

et al. 2021

In Vivo

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Background/Aim: The reproducibility of atherosclerotic lesions was evaluated after the production of clonedmicrominipigs and their offspring. Materials and Methods: Cloned-microminipig-parents were produced by microminipigsomatic cell nuclei. These parents were crossbred and delivered males (F1-offspring) were divided into two groups: normal chow diet (NcD)-fed and high-fat/high-cholesterol diet (HcD)-fed groups. One of the F1-offsprings was subjected to cloning, and delivered males (F1-clones) were fed with HcD. After 8 weeks, all animals were necropsied for pathophysiological studies compared to non-cloned-microminipigs. Results: HcD-fed F1-offspring and F1-clones, but not NcDfed F1-offspring, exhibited increased serum lipid levels and systemic atherosclerosis, which were comparable to those of HcD-fed non-cloned-microminipigs. Homogeneity of variance analysis demonstrated that standard deviation values of serum lipoprotein and aortic atherosclerosis area from HcD-fed animals decreased in F1-offspring and F1-clones. Conclusion: HcD-induced atherogenesis was highly reproducible in F1offsprings and F1-clones, indicating that the atherosclerosisprone genomic background was preserved in the clonedmicrominipigs, which can be used for studies on human atherosclerosis and related diseases.To study the pathogenesis of atherosclerosis, many animals, including mice, rats, rabbits, and swine are widely used worldwide (1). In contrast to human lipid metabolism, mice and rats are high-density lipoprotein (HDL)-cholesterol dominant in their serum lipid profiles and are essentially resistant to the high-fat/high-cholesterol diet (HcD) used to develop atherosclerosis. This is partially explained by the absence of expression of several genes that regulate lipid metabolism and atherogenesis (1-3). Therefore, gene modification, for example gene knockout of apolipoprotein E or low-density lipoprotein receptor (LDLr), is necessary to efficiently produce atherosclerosis in mice (1, 4). However, since the pathogenesis of atherosclerosis includes both genetic and environmental factors, animal models should ideally have anatomy, physiology, and life habits similar to humans (5). In this sense, swine are a potentially useful animal model for atherosclerosis research because their anatomy, physiology, lipid metabolism, and life habits are very similar to those of humans (6, 7). 2025This article is freely accessible online.

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The History of the WHHL Rabbit, an Animal Model of Familial Hypercholesterolemia (I) - Contribution to the Elucidation of the Pathophysiology of Human Hypercholesterolemia and Coronary Heart Disease -

Cited by 13 publications

References 79 publications

Strategies for Highly Efficient Rabbit Sperm Cryopreservation

Strategies for Highly Efficient Rabbit Sperm Cryopreservation

Zebrafish Model for Screening Antiatherosclerosis Drugs

High Pathological Reproducibility of Diet-induced Atherosclerosis in MicrominipigsviaCloning Technology

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