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Analysis of the lymphatic development using mutant mice

Research Project

Project/Area Number 12670294
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionThe University of Tokyo

Principal Investigator

YOSHIDA Nobuaki  The Institute of Medical Science, lab. Gene Expression and Regulation, Ctr. Exp, Med, The University of Tokyo, Professor, 医科学研究所, 教授 (10250341)

Co-Investigator(Kenkyū-buntansha) ICHISE Hirotake  The Institute of Medical Science, lab. Gene Expression and Regulation, Ctr. Exp, Med, The University of Tokyo, Research Associate, 医科学研究所, 助手 (10313090)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordslymphatic vessels / mutant mouse / lymphatic edema / transgenic mouse / LYVE-1 / マウス / lyve-1
Research Abstract

The lymphatics are thought to be responsible for edematous condition in patients, especially in patients suffering from primary lymphedema. Resent studies show that lymphangiogenesis, as well as angiogenesis, also plays some roles on tumor metastasis. However, the lymphatic development in mammals has been unknown from lack of reliable anatomical / histological procedure for the detection of lymphatic vassals and useful mutant animal that has obvious lymphatic abnormality.
In order to understand the mechanism of lymphatic development and functions, we are generating "reporter" strains by transgenesis or targeted mutagenesis, using marker genes (lacZ, GFP, PLAP) under transcriptional regulation of the lymphatic endothelial-specific genes, such as LYVE-1, prox-1 and VFGFR-3. We have cloned mouse LYVE-1 gene and determined the genomic structure and chromosomal location of the gene in mice. For the construction of the transgenes using Prox-1 gene or VEGFR-3 gene, we purchased and re-analyzed their P1 or BAC clones. We are now introducing some constructs into mouse fertilized eggs. We have also started on the conditional knockout analyses of potential growth factor / receptor and transcriptional factors in lymphangiogenesis.
We are also under investigation of an original spontaneous mutant mouse line developing chylous ascites, intestinal lymphedema and edematous hindfoot that are thought to be due to lymphatic abnormality. The blood flow is found not only in blood vessels but also in lymphatic vessels in the homozygous mutants. According to the confocal microscopic analysis of TRITC-conjigated gelatin injected into blood vessels, the peripheral capillary-lacteal shunt at the intestinal villi is one of the cause for blood flow observed lymphatics of the homozygous mutant mice. We are trying forward genetic approaches to find the candidate gene (s) for this mutation.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Honke, k., Hirahara, Y., Dupree, J., Suzuki, K., Popko, B., Fukushima, K., Fukushima, J., Nagasawa, T., Yoshida, N., Wada, Y., Taniguchi, N.: "Paranodal junction formation and spermatogenesis require sulfoglycolipids"Proc. Natl. Acad. Sci., USA. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohtsuka, S., Takaki, S., Iseki, M., Nakagata, N., Kataoka, Y., Yoshida, N., Takatsu, K., Miyoshi, K., Yoshimura, A.: "SH2-B is Required for both Male and Female Reproduction"Mol. Cell. Biol.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fukuyama, H., Adachi, M., Suematsu, S., Miwa, K., Suda, T., Yoshida, N., Nagata, S.: "Requirement of Fas expression in B cells for tolerance induction"Eur. J. Immunol.. 32. 223-230 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fukami, K., Nakao, K., Inoue, T., Kataoka, Y., Nakamura, K., Katsuki, M., Yoshida, N., Takenawa, T.: "Requirement of phosholipase Cd4 for the first step of fertilization"Science. 292. 920-923 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hirata, A., Yoshida, S., Inoue, N., Matsumoto, K., Ninomiya, A., Taniguchi, M., Matsuyama, T., Kato, K., Iizasa, H., Kataoka, Y., Yoshida, N., Shiosaka, S.: "Abnormalities of Synapses and Neurons in the Hippocampus of Neuropsin-Deficient Mice"Mol. Cell. Neurosci.. 17. 600-610 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Honke K, Hirahara Y, Dupree J, Suzuli K, Popko B, Fukushima K, Fukushima J, Nagasawa T, Yoshida N, Wada Y, Taniguchi N: "Paranodal junction formation and spermatogenesis require sulfoglycolipids"Proc. Natl. Acad. Sci., USA. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohtsuka S, Takaki S, Iseki M, Nakagata N, Kataoka Y, Yoshida N, Takatsu K, Miyoshi K, and Yoshimura A: "SH2-B is Required for both Male and Female Reproduction"Mol. Cell. Biol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fukuyama H, Adachi M, Suematsu S, Miwa K, Suda T, Yoshida N, and Nagata S: "Requirement of Fas expression in B cells for tolerance induction"Eur. J. Immunol. 32. 223-230 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fukami K, Nakao K, Inoue T, Kataoka Y, Nakamura K, Katsuki M, Yoshida N, and Takenawa T: "Requirement of phosholipase Cd4 for the first step of fertilization"Science. 292. 920-923 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hirata A, Yoshida S, Inoue N, Matsumoto K, Ninomiya A, Taniguchi M, Matsuyama T, Kato K, Iizasa H, Kataoka Y, Yoshida N, and Shiosaka S: "Abnormalities of Synapses and Neurons in the Hippocampus of Neuropsin-Deficient Mice"Mol. Cell. Neurosci. 17. 600-610 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Honke K., Hirahara Y., Dupree, J., Suzuki, K., Popko, B., Fukushima, K., Fukushima, J., Nagasawa, T., Yoshida, N., Wada, Y, Taniguchi, N.: "Paranodal junction formation and spermatogenesis require sulfoglycolipids"Proc. Natl. Acad. Sci., USA. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohtsuka, S., Takaki, S., Iseki, M., Nakagata, N., Kataoka, Y., Yoshida, N., Takatsu, K., Miyoshi, K., Yoshimura, A.: "SH2-B is Required for both Male and Female Reproduction"Mol. Cell. Biol.. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Fukuyama, H., Adachi, M., Suematsu, S., Miwa, K., Suda, T., Yoshida, N., Nagata, S.: "Requirement of Cd4 expression in B cells for tolerance induction"Eur. J. Immunol.. 32. 223-230 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fukami, K., Nakao, K., Inoue, T., Kataoka, Y., Nakamura, K., Katsuki, M., Yoshida, N., Takenawa, T.: "Requirement of phosholipase Cd4 for the first step of fertilization"Science. 292. 920-923 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hirata, A., Yoshida S, Inoue N, Matsumoto, K., Ninomiya, A., Taniguchi, K., Matsuyama, T, Kato, K., Iizasa, H., Kataoka, Y, Yoshida, N., Shiosaka, S.: "Abnormalities of Synapses and Neurons in the Hippocampus of Neuropsin-Deficient Mice"Nol. Cell. Meurosci.. 17. 600-610 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hirata,A. et al.: "Abnormalities of Synapses and Neurons in the Hippocampus of Neuropsin-Deficient Mice."Mol.Cell.Neuroscience,. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Aono,A. et al.: "Forced expression of terminal deoxynucleotidyl transferase in fetal thymus resulted in a decrease in γδT cells and random dissemination of Vγ3Vδ1 T cells in skin of newborn but not adult mice."Immunology. 99. 489-497 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Matsuoka,T. et al.: "Prostaglandin D_2 as a mediator of allergic asthma."Science. 287. 2013-2017 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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