权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Utilization of transgenic animals for applied biology

利用转基因动物进行应用生物学

基本信息

批准号：
04556042
负责人：
TAKAHASHI Michio
金额：
$ 10.43万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research (B)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1994
项目状态：
已结题

项目摘要

Since human growth hormone (hGH) gene was successfully introduced into the mouse embryo to produce the 'first transgenic animal", it has been most frequently employed in the trials of producing the farm animals of improved characteristics by means of transgenic techniques. In most cases, however, such efforts were in vain because of an arrest of embryonic development, failure of reproductive function, manifestation of metabolic disorders, etc. in animals carrying hGH gene, and unfortunately no promising results were obtained so far. To resolve these problems accompanying to produce transgenic cattles, the following investigations were undertaken in this study.1)Whey acidic protein (WAP) is a major whey protein in mammalian milk. WAP gene promoter is expected to regulate the mammary gland specific expression of structural genes. In this study, we have successfully generated transgenic mice and rats carrying a hybrid gene in which hGH gene is under the control of mouse WAP gene promoter. … More 2)The hybrid descendants between transgenic mice carrying WAP-hGH gene (BDF1) and ICR,which is known by their higher ability of producing milk among strains of mice, were obtained. It was confirmed that bioactive hGH was secreted in the milk. The transgenic animals showed obesity, diabetes and infertility. By histological examination, interesting abnormalities were found in the pituitary, gonad, adrenal and mammary glands.In female transgenic mice, mammary tumor developed after the age of 12 weeks, in which high expression of MMTV,EGF and TNF were detected. The span of life of the transgenic mice was considerably short and they should be auseful model for the study of aging.3)Two lines of transgenic rats, i.e., high-hGH line and low-hGH line, were produced.The former was characterized by high concentration of hGH in the blood, while the latter was by low concentration of it. Transgenic rats of high-hGH line showed precocious puberty, gigantism and infertility, and those of low-hGH line showed precocious puberty, obesity and infertility.Further, animals of low-hGH line also showed the interesting features similar to those of non-insulin dependent diabetes (NIDD) .Serum levels of triglyceride, free fatty acids, cholesterol, and keton bodies in the low-hGH transgenic rats were significantly higher than those of normal rats.Studies concerning obesity and NIDD in transgenic rats are being performed.hGH receptor gene was isolated from cDNA library for human liver, and a hybrid gene of metallothionein promoter and hGH receptor gene was constructed. We are now planning to produce transgenic rats expressing hGH receptor and to obtain hybrid animals expressing both hGH and its receptor.These transgenic animals would be useful experimental models for the study of GH actions and application of transgenic techniques to the farm animals. Less

自从人类生长激素（human growth hormone，hGH）基因被成功地导入小鼠胚胎中产生“第一只转基因动物”以来，hGH基因已被广泛应用于通过转基因技术生产改良性状的家畜的试验中。然而，在大多数情况下，这些努力是徒劳的，因为在携带hGH基因的动物中胚胎发育停滞、生殖功能失败、代谢紊乱的表现等，不幸的是，迄今为止没有获得有希望的结果。为了解决转基因牛生产过程中存在的问题，本研究进行了以下研究：1）乳清酸性蛋白（Whey acidic protein，WAP）是哺乳动物乳中主要的乳清蛋白。WAP基因启动子有望调控乳腺特异性表达的结构基因。在本研究中，我们已经成功地建立了转基因小鼠和大鼠携带的杂交基因，其中hGH基因是在小鼠WAP基因启动子的控制下。 ...更多信息 2)获得了WAP-hGH转基因小鼠（BDF 1）与ICR小鼠（产奶能力强）的杂交后代。结果表明，在乳汁中分泌有生物活性的hGH。转基因动物表现出肥胖、糖尿病和不育。组织学检查发现垂体、性腺、肾上腺和乳腺均出现异常，雌性转基因小鼠在12周龄后出现乳腺肿瘤，肿瘤组织中检测到MMTV、EGF和TNF的高表达。转基因小鼠寿命短，可作为研究衰老的有效模型。高hGH系转基因大鼠表现为性早熟、发育迟缓和不育，而低hGH系转基因大鼠表现为性早熟、肥胖和不育。低hGH系的动物也显示出与非胰岛素依赖型糖尿病（NIDD）相似的有趣特征。甘油三酯、游离脂肪酸、胆固醇从人肝脏cDNA文库中分离hGH受体基因，构建了金属硫蛋白启动子与hGH受体基因的杂合基因。本研究拟建立表达hGH受体的转基因大鼠和同时表达hGH及其受体的杂交动物，为研究GH的作用和转基因技术在家畜上的应用提供有用的实验模型。少