Hereditary postprandial hypertriglyceridemic rabbit model

Multicellular living organisms and unmodified parts thereof and – Nonhuman animal – The nonhuman animal is a model for human disease

Reexamination Certificate

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C800S008000, C800S014000, C800S022000, C800S003000

Reexamination Certificate

active

06515196

ABSTRACT:

BACKGROUND OF THIS MODEL
1. Subject Matter
This model relates to a novel hereditary postprandial hypertriglyceridemia rabbit, with normal serum triglyceride values under conditions of fasting and high levels of serum triglyceride, postprandially
2. Description of the Related Art
The three main causes of death worldwide are cancer, cardiac and cerebrovascular-related diseases. The number 1 cause of mortality in the United States is coronary heart disease. Accordingly, to limit the occurrence of vascular diseases is one of the most important medical challenges for the 21st century. The main underlying cause of vascular diseases is atherosclerosis. Factors closely related to the occurrence and severity of atherosclerosis have been elucidated in epidemiological studies and these factors are designated “risk factors”. Known risk factors for atherosclerotic heart disease are hyperlipidemia, hypertension, diabetes, tobacco use and gender (male, menopausal females). Hyperlipidemia includes hypercholesterolemia, hypertriglyceridemia and a combination of these lipid abnormalities.
However, in the highly industrialized countries of Europe, North America and Japan, ingestion of higher nutrient food and excessive calories on a yearly increase. Consequently, hypertriglyceridemia have emerged as a serious risk factor in common diseases or even vascular-related diseases. Mechanisms governing hypertriglyceridemia and related cardiovascular diseases have yet to be fully elucidated. The relationship between food consumption and hypertriglyceridemia has to be clearly defined. Therefore, an animal model with postprandial hypertriglyceridemia has been investigated in hopes of throwing light on the problems
SUMMARY
The objective of this invention was to design an animal model with high levels of serum lipid following ingestion of food. Hyperlipidemia is a well accelerating factor for atherosclerosis. The effect of diet on lipid and lipoprotein concentration is well established. In clinical situations where hyperlipidemia is the main pathogenesis of atherosclerosis, postprandial hyperlipidemia has been considered a serious risk factor, which aggravates vascular diseases. However, whether postprandial hyperlipidemia is acquired or is heritable in nature, the characteristics of lipid metabolism in postprandial hyperlipidemia and how and when these lipid metabolisms aggregate have not investigated systematically. The model animal designed here will be used widely as a clinical specimen to explore these questions.
The Watanabe heritable hyperlipidemic rabbit (WHHL) has hyperlipidemia, and a pure line of rabbits with heritable combined hypercholesterolemia and hypertriglyceridemia after selected inbreedings was obtained and has been designated a hereditary hypertriglyceridemic rabbit (TGH: TG=triglyceride, H=high). Hypercholesterolemia in WHHL is caused by a genetic anomaly on LDL (low-density lipoprotein) receptor. The hereditary hypertriglyceridemia rabbit was selected from a WHHL rabbit sub-line, characterized by unusual high levels of triglyceride. The workers crossed TGH and Japanese White rabbit (JW) to determine the mode inheritance and individual rabbits with hypertriglyceridemia only after ingestion of food were identified. There have been no descriptions of a model animal with the hereditary trait of hypertriglyceridemia only after ingestion of food.


REFERENCES:
Takasaki et al., A New Rabbit Strain with Heritable Hypercolesterolemia and Hypertriglycerdemia, 1998, Lippoprotein Metab. Atherog., pp. 157-159.

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