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Deveropmental biotechnological analysis of host defense mechanisms against protozoan infection

Research Project

Project/Area Number 08306019
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied veterinary science
Research InstitutionOBIHIRO UNIVERSITY OF AGRICULTURE AND VETERINARY MEDICINE

Principal Investigator

TOYODA Yutaka  The Research Center for Protozoan Molecular Immunology, OBIHIRO UNIVERSITY OF AGRICULTURE AND VETERINARY MEDICINE,Professor, 原虫病分子免疫研究センター, 教授 (90050418)

Co-Investigator(Kenkyū-buntansha) IWAKURA Yoichiro  University of Tokyo, Professor, 医科学研究所, 教授 (10089120)
TAKAHASHI Michio  University of Tokyo, Professor, 農学生命科学研究科, 教授 (30011943)
IGARASHI Ikuo  The Research Center for Protozoan Molecular Immunology, Associate Professor, 原虫病分子免疫研究センター, 助教授 (80159582)
NAGASAWA Hidiyuki  The Research Center for Protozoan Molecular Immunology, Professor, 原虫病分子免疫研究センター, 教授 (60172524)
SAITO Atushi  Department of Beterinary Medicine, Professor, 畜産学部, 教授 (10002263)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥18,800,000 (Direct Cost: ¥18,800,000)
Fiscal Year 1997: ¥9,500,000 (Direct Cost: ¥9,500,000)
Fiscal Year 1996: ¥9,300,000 (Direct Cost: ¥9,300,000)
KeywordsTransgenic / macrophage / Scavenger receptor / Interferon / Babesia / Toxoplasma / Trypanosoma / mouse / インターフエロン / ネオスポーラ原虫
Research Abstract

(l)Studies on gene knock-out mice
Experiments on the host defense mechanisms against protozoan infection were performed using a macrophage scavenger receptor (SR) knock-out mice. As the SR is known to bind an extraordinary wide range of ligands including bacterial pathogens and mediate macrophage adhesion, it would be of interest to know the response of SR knock-out mice against protozoan infection. After intraperitoneal inoculation with Babesia microti, parasitemia was monitored daily by counting parasitized erythrocytes.
It was found that the course of parasitemia was not different between SR-/- and SR+/+ mice but the decrease in packed cell volume at 16-30 days after infection was less obvious in SR-/- than in SR+/+ mice. Increase in spleen weight after B.microti infection was also smaller in SR-/- than in SR+/+ mice. Flow cytometric studies revealed that the percentages of Thy 1.2+ as well as CD4+ T cells in spleen remained relatively higher in SR-/- mice as compared to those in SR+/ … More + mice after infection. These results suggest that the SR knock-out mouse may become a useful model for the analysis of protozoan infection, especially with regard to the recovery processes, although it seems not to be directly involved in the defense mechanisms against B.microti infection.
Studies using other types of knock-out mice, such as IFN gamma and iNOS, were also conducted.
(2) Production of transgenic mice carrying protozoan gene
SAG-i (p30), the major surface protein of Toxoplasma gondii, is considered as an important ligand in the process of host cell invasion. If this protein is produced by host cells and interfere with that of parasites, then the host will become resistant to parasite invasion, Or, it may become more susceptible to infection due to the lack of immune response against p30 antigen. To generate transgenic mice carrying p30 gene, a 3.3kb DNA fragments, containing p30 cDNA fused with CAG promoter, that has been shown to direct a ubiquitous expression of a reporter gene in transgenic mice, were microinjected into one of the pronuclei of one-cell embryos of C57BL/6J, BALB/c or F1 (C57BL/6J x C3H/He) mice. The embryos were transferred to the oviducts of pseudopregnant ICR mice, In the first series of experiment using inbred strains, two p30-positive founders (male C57BL/6J and female BALB/c) were obtained among 159 mice that developed from the injected eggs. Furthermore, we have obtained several P30-founder mice expressing the gene product and transmitting the gene to the next generation, by using F1 (C57BL/6J x C3H/He) embryos. As far as we are aware, this is the first transgenic mice bearing a protozoan gene derived from T.gondii. Less

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Kamada,T.et al.: "The role of scavenger receptor type A (SR-A) during infection with Babesia microti." J.Protozool.Res.7(3). 81-89 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Remer,K.et al.: "Different activation of lymphocytes in reaction to Babesia microti in iNOS-l- and wild type mice." J.Protozool.Res.7(2). 63-69 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Suzuki,H.et al.: "A role for macrophage scavenger receptors in artherosclerosis and susceptibility to infection." Nature. 386(6622). 292-296 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Suzuki,H.et al.: "The multiple roles of macrophage scavenger receptors (MSR) in vivo:Resistance to artherosclerosis and susceptibility to infection in MSR knockout mice." J.Artheroscler.Thrombosis. 4(1). 1-11 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Choi,Y-H.et al.: "Effect of taurine on in vitro fertilization and embryo development of BALB/c mouse strain." J.Reprod.Dev.44(1). 29-34 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Choi,Y-H.et al.: "Capacitation and fertilizing ability of BALB/c mouse spermatozoa collected from different regions of cauda epididymis." J.Reprod.Dev.44(3). 261-266 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kamada, T., Igarashi, I., Inoue, N., Nagasawa, H., Suzuki, H., Kodama, T., Suzuki, N.and Toyoda, Y.: "The role of scavenger receptor type A (SR-A) during infection with Babesia microti" J.Protozool.Res.7 (3). 81-89 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Remer, K., Igarashi, I., Inoue, N., Nagasawa, H., Toyoda, Y.and Suzuki, N.: "Different activation of lymphocytes in reaction to Babesia microti in iNOS-/-and wild type mice." J.Protozool.Res.7 (2). 63-69 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Suzuki, H., Kurihara, Y., Takeya, M., Kamada, N., Kataoka, M., Jishage, K., Ueda, O., Sakaguchi, H., Higashi, T., Suzuki, S., Takashima, Y., Kawabe, Y., Cynshi, O., Wada, Y., Honda, M., Kurihara, H., Aburatani, H., Doi, T., Matsumoto, A., Azuma, S., Noda, T., Toyoda, Y., Itakura, H., Yazaki, Y., Horiuchi, S., Takahashi, K., Kruijt, J.K., vanBerkel, T.J.C., Steinbrecher, U.P., Ishibashi, S., Maeda, N., Gordon, S.and Kodama, T.: "A role for amcrophage scavenger receptors in artherosclerosis and susceptibility to infection." Nature. 386 (6622). 292-296 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Suzuki, H., Kurihara, Y., Takeya, M., Kamada, N., Kataoka, M., Jishage, K., Sakaguchi, H., Kruijt, J.K., Higashi, T., Suzuki, T., vanBerkel, T.J.C., Horiuchi, S., Takahashi, T., Yazaki, Y.and Kodama, T.: "The multiple roles of macrophage scavenger receptors (MSR) in vivo : Resistance to artherosclerosis and susceptibility to infection in MSR knockout mice." J.Artheroscler.Thrombosis. 4 (1). 1-11 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Choi, Y-H., Seng, S.and Toyoda, Y.: "Effect of taurine on in vitro fertilization and embryo development of BALB/c mouse strain." J.Reprod.Dev.44 (1). 29-34 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Choi, Y-H., Seng, S., Boonchit, S.and Toyoda, Y.: "Capacitation and fertilizing ability of BALB/c mouse spermatozoa collected from different regions of cauda epididymis." J.Reprod.Dev.44 (3). 261-266 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Suzuki,H.et al.: "A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection" Nature. 386・6622. 292-296 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Asano,M.et al.: "Growth retardation and early death of β-1,4-galactosyltransferase knockout mice with augmented proliferation and abnormal differentiation" EMBO Journal. 16・8. 1850-1857 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tagawa,Y.et al.: "Suppression of concanavalin A-induced hepatitis in IFN-γ-/-mice,but not in TNF-α-/-mice" Journal of Immunology. 159・3. 1418-1428 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Choi,Y-H.et al.: "Effect of taurine on in vitro fertilization and embryo development of BALB/c mouse strain" Journal of Reproduction and Development. 44・1(印刷中). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Seng,S.et al.: "Production of transgenic mice carrying p30 gene encoding major surface antigen of Toxoplasma goηdii" Journal of Protozoology Research. (印刷中). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tsukui,T.et al.: "Transgenesis by adenovirus-mediated gene transfer into mouse zona-free eggs" Nature Biotechnology. 14・8. 982-985 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Meno,C.et al.: "Left-right asymmetric expression of the TGF β-family member Lefty in mouse embryos" Nature. 381・6578. 151-155 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Araki,K.et al.: "Meiotic abnormalities of c-mos knockout mouse oocytes : activation after first meiosis or entrance into third meiotic metaphase" Biology of Reproduction. 55・6. 1315-1324 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Haraguchi,S.: "Effects of phosphate on the in vitro 2-cell block of AKR/N mouse embryos based on changes in cdc2 kinase activity and phosphorylation" Biology of Reproduction. 55・3. 598-603 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Suzuki,H.et al.: "A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection" Nature 印刷中. (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Asano,M.et al.: "Growth relardation and early death of β-1,4-galactosyltransferase knockout mice with augmented proliferat in and abnormal differentiation" EMBO Journal 印刷中. (1997)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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