2000 Fiscal Year Final Research Report Summary
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
|
| Keywords | B cell / signal transduction / α4 / BCR / immune response / rapamycin / conditional gene targeting |
|---|
| 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.
|
