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Characterization of physiological function of the plasma proteins, PFBP and IHRP with knockout mice.

敲除小鼠血浆蛋白、PFBP 和 IHRP 生理功能的表征。

基本信息

批准号：
11470489
负责人：
TOMITA Motowo
金额：
$ 9.41万
依托单位：
Showa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470489/
关键词：
Knockout mice Plasma protein PHBP IHRP Serine Protease GBP-28 Adiponectin ES細胞トランスゲニックマウス

项目摘要

1) Studies on PHBPPHBP (Plasma Hyaluronan-Binding Protein)was found from human blood plasma by our group in 1996.PHBP contains three EGFs, a Kringle and a serine protease domains, and is activated to reveal proteolytic activity when a specific peptide bond is cleaved. To elucidate its functions, we tried to produce PHBP gene knockout mice. After the genomic structure of mouse PHBP gene was determined, a targeting vector was constructed to substitute a neomycin tolerant gene for a 1 kb region of the first exon. Since an ES cell clone which was knockout with PHBP gene was produced, we are trying to produce the knockout mice.2) Studies on IHRPIHRP(Inter a trypsin inhibitor Heavy chain Related Protein)was found from human blood plasma by our group in 1996.About 70% of IHRP has homology in amino acid sequence to ITT heavy chain while IHRP does not show the trypsin-inhibiting activity which ITT shows. As functions of THRP has been elucidated yet, we also tried to produce IHRP gene knockout mice. Presently we have determined the structure of mouse IHRP gene as well as the nucleotide sequence of mouse IHRP mRNA.3) Studies on GBP 28While we were working with PHBP and IHRP, we also found GBP 28 from human blood plasma. GBP 28 (gelatin binding protein of 28 kd) was the translated product of apM1 mRNA which was found as an adipocyte specific mRNA by Matsuzawa et al (Osaka univ.). Matsuzawa named this protein adiponectin later. In 2001, GBP 28/adiponectin was found to have a possibility for an anti diabetes drug. Presently we are also trying to produce IHRP-gene-knockout mice.

1）PHBP的研究PHBP（血浆透明质酸结合蛋白）是我们课题组于1996年从人血浆中发现的。PHBP含有三个EGF、一个Kringle和一个丝氨酸蛋白酶结构域，当特定的肽键被裂解时被激活，显示出蛋白水解活性。为了阐明其功能，我们尝试制备 PHBP 基因敲除小鼠。确定小鼠PHBP基因的基因组结构后，构建靶向载体，用新霉素耐受基因替换第一个外显子的1 kb区域。自从制作出敲除PHBP基因的ES细胞克隆后，我们正在尝试制备敲除小鼠。2）IHRPIHRP（胰蛋白酶抑制剂重链相关蛋白）的研究是我们课题组于1996年从人血浆中发现的。IHRP中约70%的氨基酸序列与ITT重链具有同源性，而IHRP并不表现出ITT所表现出的胰蛋白酶抑制活性。由于THRP的功能尚未阐明，我们还尝试制备IHRP基因敲除小鼠。目前我们已经确定了小鼠IHRP基因的结构以及小鼠IHRP mRNA的核苷酸序列。3）GBP 28的研究在我们研究PHBP和IHRP的同时，我们还从人血浆中发现了GBP 28。 GBP 28（28 kd 明胶结合蛋白）是 apM1 mRNA 的翻译产物，Matsuzawa 等人（大阪大学）发现其为脂肪细胞特异性 mRNA。松泽后来将这种蛋白质命名为脂联素。 2001年，GBP 28/脂联素被发现有可能成为抗糖尿病药物。目前我们也在尝试培育IHRP基因敲除小鼠。