1999 Fiscal Year Final Research Report Summary
Functional analysis of Id protein using "knock-out" mice
| Project/Area Number |
10670119
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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 |
General medical chemistry
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
YOKOTA Yoshifumi Kyoto Univ., Graduate Sch. Medicine Associate Professor, 医学研究科, 助教授 (50222386)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Id / bHLH factor / cell differentiation / growth control / natural killer cell / KO mice / mammary gland |
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| Research Abstract |
Transcription factors bearing a basic helix-loop-helix (bHLH) motif play essential roles in many cell differentiation processes during development of multicellular organisms. These factors are negatively regulated at the protein level by Id, inhibitors of DNA binding/differentiation. To investigate in vivo functions of Id proteins, we generated mice lacking Id2 and analyzed their phenotypes. The following findings were obtained :
1) Id2-deficient mice lack lymph nodes and Peyer's patches, and show greatly reduced population of natural killer (NK) cells. Defective secondary lymphoid organ is due to a lack of the CD4+CD3-IL-7Ra+cell population. Impaired NKcell development is observed even in the fetal thymus and is derived from intrinsic problem in common bipotent T/NK progenitors.
2) Id2-deficent mice show greatly elevated serum IgE level, which is partly due to increased Th2 responses.
3) Id2-deficent mice have a lactation defect and can not support their pups. This phenotype is derived from impaired cell proliferation in mammary epithelial cells in response to hormonal stimuli caused by pregnancy.
4) We isolated a novel bHLH factor that has an inhibitory activity similar to that of Id.
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[Publications] Mori, S., Sugawara, S., Kikuchi, T., Tanji, M., Narumi, O., Stoykova, A., Nishikawa, S.-I., and Yokota, Y.: "The leukemic oncogene tal-2 is expressed in the developing mouse brain."Mol. Brain Res.. 64. 199-210 (1999)
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[Publications] Yokota, Y., Mansouri, A., Mori, S., Sugawara, S., Adachi, S., Nishikawa, S.-I., and Gruss, P.: "Development of peripheral lymphoid organs and natural killer cells depends on the helix-loop-helix inhibitor Id2."Nature. 397. 702-706 (1999)
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[Publications] Narumi, O., Mori, S., Boku, S., Tsuji, Y., Hashimoto, N., Nishikawa, S.-I. and Yokota, Y.: "OUT, a novel basic helix-loop-helix transcription factor with and Id-like inhibitory activity."J. Biol. Chem.. 275. 3510-3521 (2000)
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[Publications] Kataoka, H., Murayama, T., Yokode, M., Mori, S., Sano, H., Ozaki, H., Yokota, Y., Nishikawa, S.-I. and Kita, T.: "A novel Snail-related transcription factor Smuc regulates basic helix-loop-helix transcription factor activities via specific E-box motifs."Nucleic Acids Res.. 28. 626-633 (2000)
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