Establishment of genetic lipid storage disease with lysosomal acid lipase deficiency in rats

溶酶体酸性脂肪酶缺乏遗传性脂质沉积病大鼠的建立

• 批准号: 63480144
• 负责人: YOSHIDA Hiroki
• 金额: $ 2.24万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-63480144/
• 关键词: Cholesterol Ester; Triglyceride; Acid Lipase; Rat; コレステロールエステル

We established a new animal model of a genetic lipid storage disease analogous to human Wolman's disease. Affected Donryu rats, who inherited the disease in an autosomal recessive mode, manifested marked hepatosplenomegaly, lymph node enlargement, and thickened, dilated intestine. Morphologically, many characteristic foam cells Were observed in livers and spleens. No adrenal calcification could be found in affected rats. Biochemical studies on spleen and liver tissues showed massive accumulation of esterified cholesterol and triglycerides and deficiency of acid lipase for [^<14>C] -triolen, [^<14>C]-cholesterol oleate, and 4-methylumbelliferyl oleate.This animal model could contribute greatly to the clarification of the physiological and pathological roles of lysosomal acid lipase in the metabolism of lipoproteins and cholesterol, and of the pathogeneisis of atherosclerosis.

我们建立了一种类似人类沃尔曼病的遗传性脂质储存病的新动物模型。受影响的东流大鼠以常染色体隐性模式遗传该疾病，表现为明显的肝脾肿大，淋巴结肿大，肠增厚，扩张。在形态学上，肝脏和脾脏中可见许多特征性泡沫细胞。大鼠肾上腺未见钙化。脾脏和肝脏组织的生化研究显示，酯化胆固醇和甘油三酯大量积聚，[^<14>C]-三烯、[^<14>C]-油酸胆固醇和4-甲基伞叶油酸酯的酸性脂肪酶缺乏。该动物模型有助于阐明溶酶体酸性脂肪酶在脂蛋白和胆固醇代谢中的生理病理作用以及动脉粥样硬化的发病机制。

项目成果

Hiroki Yoshida,et al.: "Genetic lipid storage disease with lysosomal acid lipase deficiency in rats." Laboratory Animal Science(印刷中). (1990)

Hiroki Yoshida 等人：“大鼠溶酶体酸性脂肪酶缺乏症的遗传性脂质储存病”（实验动物科学）（1990 年）。

Masaru Kuriyama, Hiroki Yoshida, et al.: "Lysosomal acid lipase deficiency in rats ; Lipids analyses and lipase activities in livers and spleens." Biochemica et Biophysica Acta.

Masaru Kuriyama、Hiroki Yoshida 等人：“大鼠溶酶体酸性脂肪酶缺乏症；肝脏和脾脏中的脂质分析和脂肪酶活性。”

Masaru Kuriyama,Hiroki Yoshida,el al.: "Lysosomal acid lipase deficiency in rats;Lipid analyses and lipases activities in livers and spleens." Biocemica et Biophysica Acta.

Masaru Kuriyama、Hiroki Yoshida 等人：“大鼠溶酶体酸性脂肪酶缺乏症；肝脏和脾脏中的脂质分析和脂肪酶活性。”

Hiroki Yoshida,Aichi Yoshida, et al.: "Lyosomal acid lipase deficiency in rats;Immunohistochemical and electron microscopic studies." Amirican Journal of Pathology(投稿予定).

Hiroki Yoshida、Aichi Yoshida 等人：“大鼠溶酶体酸性脂肪酶缺乏症；免疫组织化学和电子显微镜研究。”美国病理学杂志（待提交）。

Hiroki Yoshida;Masaru Kuriyama;Aichi Yoshida;Akihiro Igata.: The American Journal of Pathology.

Hiroki Yoshida；Masaru Kuriyama；Aichi Yoshida；Akihiro Igata。：美国病理学杂志。