2002 Fiscal Year Final Research Report Summary
Mechanisms underlying the integration of cell differentiation and proliferation by Id proteins
| Project/Area Number |
13470034
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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 |
Pathological medical chemistry
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| Research Institution | Fukui Medical University |
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Principal Investigator |
YOKOTA Yoshifumi Fukui Medical Univ., Faculty of Medicine, Professor, 医学部, 教授 (50222386)
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| Co-Investigator(Kenkyū-buntansha) |
MORI Seiichi Fukui Medical Univ., Faculty of Medicine, Research Associate, 医学部, 助手 (10334814)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Id2 / differentiation / proliferation / KO mouse / behavioral anormaly / mammary gland / immune cells |
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| Research Abstract |
Id2 is a negative regulator of bHLH transcription factors and participate in the regulation of cell differentiation and proliferation. The aim of this project is to elucidate the mechanisms underlying the regulation of cell differentiation and proliferation through the analyses of phenotypes found in Id2-deficient mice. The phenotypes include behavioral anormaly, lactation defect and impaired differentiation of immune cells.
1. The central nervous system
We failed to detect histological alteration in the substantia nigra and striatum of Id2 KO mice. In situ hybridization analyses for neurogenic bHLH factors identified enhanced and widened expression of Math2 in the cerebral cortex of embryos on day 11.5, while other bHLH factors such as Mash1 and neurogenin2. At the same time point, immunohistochemistry using the Ki67 antibody revealed the decreased proliferation neural cells in the ventricular zone. In the adult, there was no significant alteration of the number and distribution of GABA
… More
ergic neurons in the substantia nigra and striatum. However, electrophysiological assays identified increased spontaneous firing rate of GABAergic neurons in the pars reticulata of the substantia nigra (1.3 fold), compared to that of the control littermates.
2. Mammary glands
To know an in vivo role of Id2 in cell cycle regulation, we crossed Id2 KO mice with other genetically modified mouse lines and analyzed whether the lactation defect in Id2 KO mice was rescued. However, cossing with transgenic mice bearing cyclin D1 under the control of the mouse mammary tumor virus (MMTV) promoter or p27 KO mice did not rescue the phenotype of Id2 KO mice.
3. The immune system
We found that Id2 KO mice lack the nasopharyngeal lymphoid tissue. In addition, we succeeded the reconstitution of the tissue by transferring lymphotoxin-expressing cells into Id2 KO mice. Furthermore, Id2 KO mice wererevealed to be in the Th2 dominant state due to a selective and prominent defect in CD8α+ dendritic cell subset. In B cells, Id2 was found to play an important role in suppressing the class switch to IgE. Less
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