## Transgenic Rabbits for Human Disease Models
In fact, thus far, more than 20 genes related to lipid metabolism and atherosclerosis have been introduced into transgenic rabbits (Table 2). Transgenic rabbits have also been used as disease models for cardiac failure (hypertrophic cardiomyopathy and proarrhythmic), immunology (immunity to viral infection, humoral immune response, and transplantation), and oncogenesis because of the physiological features of laboratory rabbits. The most important physiological feature of rabbits is that they have a similar lipid metabolic system to humans, whereas the mouse is quite different (Table 3) [3; 4; 5]. In mice, the major lipoproteins in plasma are high density lipoprotein (HDL) owing to the lack of cholesterol ester transfer protein. Furthermore, because rabbits do not have hepatic apolipoprotein-(apo)B mRNA editing activity, rabbit apoB-48 is only present in intestinally derived chymolicrons, which is similar to humans, unlike mice and rats in which apoB-48 is contained in both chylomicrons and hepatatically derived very low density lipoprotein and low density lipoprotein (LDL). There are other differences between humans, rabbits, and mice, such as the localized patterns of hepatic lipase (HL), an important enzyme in the metabolism of chylomicron remnants, and HDL. In humans and rabbits, HL is bound to a proteoglycan on the surface of hepatic or endothelial cells, whereas 70% or more HL in mice is in its free state and is released into blood without binding to the cell surface. Therefore, mice are resistant to cholesterol-rich diets and have difficulty in developing hypercholesterolemia and atherosclerosis. The characteristic details of transgenic rabbit models for lipid metabolism and atherosclerosis have been described in several reviews [3; 7; 8]. Interestingly, among these reviews, [PERSON] and [PERSON] [3] mentioned that phenotypes are different between mice and rabbits even when the same genes are introduced. For example, the expression of either human HL or lecithin cholesterol acyltransferase (LCAT) induces enhanced lesion formation in transgenic mice but protects against atherosclerosis in rabbits. Overexpression of apoE in mice inhibits atherosclerosis but leads to increased plasma LDL and spontaneous atherosclerosis in transgenic rabbits. High expression of human lipoprotein lipase results in myopathy in transgenic mice but not in transgenic rabbits. These observations strongly suggest that the difference in the physiological background among species affects the result of studies using human disease animal models. To extrapolate results from animal experimentation to humans, we must focus on the appropriate species depending on the purpose of the study. In addition to lipid metabolism, the myocardium composition of rabbits is also similar to that of humans (Table 3). In the human heart, \(\beta\)-myosin heavy chain (\(\beta\)-MyHC) comprises 90% of total myofibrillar myosin. In the rabbit heart, similarly to humans, 80% consists of \(\beta\)-MyCH in contrast to the mouse heart predominated by the other myosin isoform, \(\alpha\)-myosin heavy chain (\(\alpha\)-MyCH), at 95% [9; 117]. These physiological features of the rabbit can be useful for human disease models of cardiac failure, such as hypertrophic cardiopathy and proarrhythmia. To date, novel transgenic rabbits have been continuously produced and used as human disease models in lipid metabolism and atherosclerosis. Unique transgenic rabbit models have also been reported in other research areas such as Rhodopsin P347L transgenic rabbits for retinitis pigmentosa [113] and Ovine PrP transgenic rabbit for prion disease [112; 116] (Table 2). In the future, it is expected that the use of transgenic rabbits will expand to various research fields except for lipid metabolism, atherosclerosis, and cardiac failure.