2001 Fiscal Year Final Research Report Summary
Analysis of the lymphatic development using mutant mice
| Project/Area Number |
12670294
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | The University of Tokyo |
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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)
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| 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)
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| Project Period (FY) |
2000 – 2001
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| Keywords | lymphatic vessels / mutant mouse / lymphatic edema / transgenic mouse / LYVE-1 |
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| 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.
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Research Products
(10 results)
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[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
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[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
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[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
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[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
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[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
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[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
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[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
