Functional analysis of a signal transducer α4 by conditional gene targeting
Project/Area Number |
11670326
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Immunology
|
Research Institution | KUMAMOTO UNIVERSITY |
Principal Investigator |
INUI Seiji Kumamoto University, School of Medicine, Associate Professor, 医学部, 助教授 (70243384)
|
Project Period (FY) |
1999 – 2000
|
Project Status |
Completed (Fiscal Year 2000)
|
Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
Keywords | B cell / signal transduction / α4 / BCR / immune response / rapamycin / conditional gene targeting / プロテインフォスファターゼ2A / 抗原レセプター / 遺伝子破壊 / alpha 4 |
Research Abstract |
Alpha4 has been suggested to mediate BCR-signals through a rapamycin-sensitive pathway. To investigate the function of α4 in the immune response, we disrupted the α4 gene specifically in B cells. α4 floxed mice which have loxP sites upstream of exon 1 and downstream of exon 2 were established and crossed with CD19-Cre mice in which the cre cDNA is inserted into the mouse CD19 gene by knockin approach. Mutant CD19-α4-mice showed decreased number of immature and mature B cells in bone marrow and peripheral lymphoid organs. α4-B cells showed an impairment of BCR-induced proliferation accompanied by reduced S6K activation. Rapamycin sensitivity was slightly reduced in α4-B cells compared to WT B cells. The α4-mice showed impaired Ab responses to TI-and TD-Ags. These results show that α4 plays a pivotal role in the B cell activation signal transduction pathway.
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Report
(3 results)
Research Products
(12 results)