2001 Fiscal Year Final Research Report Summary
Characterization of physiological function of the plasma proteins, PFBP and IHRP with knockout mice.
| Project/Area Number |
11470489
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Showa University |
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Principal Investigator |
TOMITA Motowo Showa University, Department of Pharmaceutical Sciences, Professor, 薬学部, 教授 (30102370)
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| Project Period (FY) |
1999 – 2001
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| Keywords | Knockout mice / Plasma protein / PHBP / IHRP / Serine Protease / GBP-28 / Adiponectin |
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| Research Abstract |
1) Studies on PHBP
PHBP (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 IHRP
IHRP(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 28
While 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.
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